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2000
Volume 32, Issue 15
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

RNA modifications have recently gained great attention due to their extensive regulatory effects in a wide range of cellular networks and signaling pathways. In cardiovascular diseases (CVDs), several RNA changes, called “epitranscriptome” alterations, are found in all RNA molecules (tRNA, rRNA, mRNA, and ncRNAs). Unlike the epigenetic process, which influences the progression of atherosclerosis (AS), its transcriptional and post-transcriptional regulatory mechanisms are still unknown. Here, we described the main epitranscriptome signs to provide new insights into AS, including m6A, m5C, m1A, m7G, Ψ, and A-to-I editing. Moreover, we also included all current known RNA- modifier-targeting, including small molecular inhibitors or activators, mainly designed against m6A- and m5A-related enzymes, such as METTL3, FTO, and ALKBH5. Finally, since only a few drugs, such as azacitidine and tazemetostat, targeting the DNA epigenome, have been approved by the FDA, the next challenge would be to identify molecules for targeting the RNA epitranscriptome. To date, total Panax notoginseng total saponin could reduce vascular hyperplasia Wilms’ tumor-associated protein-1 m6A-dependent. Indeed, a virtual screening allowed us to individuate a phytomolecule, the rhein, which acts as an FTO inhibitor by increasing mRNA m6A levels. In this review, we highlighted the RNA epitranscriptome pathways implicated in AS, describing their biological functions and their connections to the disease. The identification of epitranscriptome-sensitive pathways could provide novel opportunities to find predictive, diagnostic, and prognostic biomarkers for precision medicine.

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References

  1. ZhaoB.S. RoundtreeI.A. HeC. Post-transcriptional gene regulation by mRNA modifications.Nat. Rev. Mol. Cell Biol.2017181314210.1038/nrm.2016.13227808276
    [Google Scholar]
  2. ZhaoL.Y. SongJ. LiuY. SongC.X. YiC. Mapping the epigenetic modifications of DNA and RNA.Protein Cell2020111179280810.1007/s13238‑020‑00733‑732440736
    [Google Scholar]
  3. TudekA. SchmidM. JensenT.H. Escaping nuclear decay: The significance of mRNA export for gene expression.Curr. Genet.201965247347610.1007/s00294‑018‑0913‑x30515529
    [Google Scholar]
  4. BoccalettoP. StefaniakF. RayA. CappanniniA. MukherjeeS. PurtaE. KurkowskaM. ShirvanizadehN. DestefanisE. GrozaP. AvşarG. RomitelliA. PirP. DassiE. ConticelloS.G. AguiloF. BujnickiJ.M. MODOMICS: A database of RNA modification pathways. 2021 update.Nucleic Acids Res.202250D1D231D23510.1093/nar/gkab108334893873
    [Google Scholar]
  5. DominissiniD. RechaviG. Epitranscriptome regulation.Nat. Struct. Mol. Biol.201810.1038/s41594‑018‑0140‑730266930
    [Google Scholar]
  6. MeyerK.D. SaletoreY. ZumboP. ElementoO. MasonC.E. JaffreyS.R. Comprehensive analysis of mRNA methylation reveals enrichment in 3′ UTRs and near stop codons.Cell201214971635164610.1016/j.cell.2012.05.00322608085
    [Google Scholar]
  7. KadumuriR.V. JangaS.C. Epitranscriptomic code and its alterations in human disease.Trends Mol. Med.2018241088690310.1016/j.molmed.2018.07.01030120023
    [Google Scholar]
  8. ChenJ. NingY. ZhangH. SongN. GuY. ShiY. CaiJ. DingX. ZhangX. METTL14-dependent m6A regulates vascular calcification induced by indoxyl sulfate.Life Sci.201923911703410.1016/j.lfs.2019.11703431697949
    [Google Scholar]
  9. ZhuW. ZhangH. WangS. Vitamin D3 suppresses human cytomegalovirus-induced vascular endothelial apoptosis via rectification of paradoxical m6a modification of mitochondrial calcium uniporter mRNA, which is regulated by METTL3 and YTHDF3.Front. Microbiol.20221386173410.3389/fmicb.2022.86173435359726
    [Google Scholar]
  10. LeptidisS. PapakonstantinouE. DiakouK. PierouliK. MitsisT. DragoumaniK. BacopoulouF. SanoudouD. ChrousosG. VlachakisD. Epitranscriptomics of cardiovascular diseases (Review).Int. J. Mol. Med.2021491910.3892/ijmm.2021.506434791505
    [Google Scholar]
  11. PatrassoE.A. RaikundaliaS. ArangoD. Regulation of the epigenome through RNA modifications.Chromosoma2023132323124610.1007/s00412‑023‑00794‑737138119
    [Google Scholar]
  12. ZaccaraS. RiesR.J. JaffreyS.R. Reading, writing and erasing mRNA methylation.Nat. Rev. Mol. Cell Biol.2019201060862410.1038/s41580‑019‑0168‑531520073
    [Google Scholar]
  13. ZhangW. SongM. QuJ. LiuG.H. Epigenetic modifications in cardiovascular aging and diseases.Circ. Res.2018123777378610.1161/CIRCRESAHA.118.31249730355081
    [Google Scholar]
  14. ZhangX. LiX. JiaH. AnG. NiJ. The m6A methyltransferase METTL3 modifies PGC-1α mRNA promoting mitochondrial dysfunction and oxLDL-induced inflammation in monocytes.J. Biol. Chem.2021297310105810.1016/j.jbc.2021.10105834375639
    [Google Scholar]
  15. YouY. FuY. HuangM. ShenD. ZhaoB. LiuH. ZhengY. HuangL. Recent advances of m6A demethylases inhibitors and their biological functions in human diseases.Int. J. Mol. Sci.20222310581510.3390/ijms2310581535628623
    [Google Scholar]
  16. KumariR. DuttaR. RanjanP. SuleimanZ.G. GoswamiS.K. LiJ. PalH.C. VermaS.K. ALKBH5 regulates SPHK1-dependent endothelial cell angiogenesis following ischemic stress.Front. Cardiovasc. Med.2022881730410.3389/fcvm.2021.81730435127873
    [Google Scholar]
  17. TrixlL. LusserA. The dynamic RNA modification 5-methylcytosine and its emerging role as an epitranscriptomic mark.Wiley Interdiscip. Rev. RNA2019101e151010.1002/wrna.151030311405
    [Google Scholar]
  18. SendincE. ShiY. RNA m6A methylation across the transcriptome.Mol. Cell202383342844110.1016/j.molcel.2023.01.00636736310
    [Google Scholar]
  19. RoostC. LynchS.R. BatistaP.J. QuK. ChangH.Y. KoolE.T. Structure and thermodynamics of N6-methyladenosine in RNA: A spring-loaded base modification.J. Am. Chem. Soc.201513752107211510.1021/ja513080v25611135
    [Google Scholar]
  20. FuY. JiaG. PangX. WangR.N. WangX. LiC.J. SmemoS. DaiQ. BaileyK.A. NobregaM.A. HanK.L. CuiQ. HeC. FTO-mediated formation of N6-hydroxymethyladenosine and N6-formyladenosine in mammalian RNA.Nat. Commun.201341179810.1038/ncomms282223653210
    [Google Scholar]
  21. LiuJ. YueY. HanD. WangX. FuY. ZhangL. JiaG. YuM. LuZ. DengX. DaiQ. ChenW. HeC. A METTL3–METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation.Nat. Chem. Biol.2014102939510.1038/nchembio.143224316715
    [Google Scholar]
  22. OerumS. MeynierV. CatalaM. TisnéC. A comprehensive review of m6A/m6Am RNA methyltransferase structures.Nucleic Acids Res.202149137239725510.1093/nar/gkab37834023900
    [Google Scholar]
  23. ZhengG. DahlJ.A. NiuY. FedorcsakP. HuangC.M. LiC.J. VågbøC.B. ShiY. WangW.L. SongS.H. LuZ. BosmansR.P.G. DaiQ. HaoY.J. YangX. ZhaoW.M. TongW.M. WangX.J. BogdanF. FuruK. FuY. JiaG. ZhaoX. LiuJ. KrokanH.E. KlunglandA. YangY.G. HeC. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility.Mol. Cell2013491182910.1016/j.molcel.2012.10.01523177736
    [Google Scholar]
  24. AlarcónC.R. GoodarziH. LeeH. LiuX. TavazoieS. TavazoieS.F. HNRNPA2B1 Is a mediator of m6A-dependent nuclear RNA processing events.Cell201516261299130810.1016/j.cell.2015.08.01126321680
    [Google Scholar]
  25. RoundtreeI.A. LuoG.Z. ZhangZ. WangX. ZhouT. CuiY. ShaJ. HuangX. GuerreroL. XieP. HeE. ShenB. HeC. YTHDC1 mediates nuclear export of N6-methyladenosine methylated mRNAs.eLife20176e3131110.7554/eLife.3131128984244
    [Google Scholar]
  26. FustinJ.M. DoiM. YamaguchiY. HidaH. NishimuraS. YoshidaM. IsagawaT. MoriokaM.S. KakeyaH. ManabeI. OkamuraH. RNA-methylation-dependent RNA processing controls the speed of the circadian clock.Cell2013155479380610.1016/j.cell.2013.10.02624209618
    [Google Scholar]
  27. JiangD. SunM. YouL. LuK. GaoL. HuC. WuS. ChangG. TaoH. ZhangD. DNA methylation and hydroxymethylation are associated with the degree of coronary atherosclerosis in elderly patients with coronary heart disease.Life Sci.201922424124810.1016/j.lfs.2019.03.02130867120
    [Google Scholar]
  28. YangX. YangY. SunB.F. ChenY.S. XuJ.W. LaiW.Y. LiA. WangX. BhattaraiD.P. XiaoW. SunH.Y. ZhuQ. MaH.L. AdhikariS. SunM. HaoY.J. ZhangB. HuangC.M. HuangN. JiangG.B. ZhaoY.L. WangH.L. SunY.P. YangY.G. 5-methylcytosine promotes mRNA export - NSUN2 as the methyltransferase and ALYREF as an m5C reader.Cell Res.201727560662510.1038/cr.2017.5528418038
    [Google Scholar]
  29. SchumannU. ZhangH.N. SibbrittT. PanA. HorvathA. GrossS. ClarkS.J. YangL. PreissT. Multiple links between 5-methylcytosine content of mRNA and translation.BMC Biol.20201814010.1186/s12915‑020‑00769‑532293435
    [Google Scholar]
  30. KhoddamiV. YerraA. MosbrugerT.L. FlemingA.M. BurrowsC.J. CairnsB.R. Transcriptome-wide profiling of multiple RNA modifications simultaneously at single-base resolution.Proc. Natl. Acad. Sci. USA2019116146784678910.1073/pnas.181733411630872485
    [Google Scholar]
  31. FloresJ.V. Cordero-EspinozaL. Oeztuerk-WinderF. Andersson-RolfA. SelmiT. BlancoS. TailorJ. DietmannS. FryeM. Cytosine-5 RNA methylation regulates neural stem cell differentiation and motility.Stem Cell Reports20178111212410.1016/j.stemcr.2016.11.01428041877
    [Google Scholar]
  32. Van HauteL. LeeS.Y. McCannB.J. PowellC.A. BansalD. VasiliauskaitėL. GaroneC. ShinS. KimJ.S. FryeM. GleesonJ.G. MiskaE.A. RheeH.W. MinczukM. NSUN2 introduces 5-methylcytosines in mammalian mitochondrial tRNAs.Nucleic Acids Res.201947168720873310.1093/nar/gkz55931276587
    [Google Scholar]
  33. WnukM. SlipekP. DziedzicM. LewinskaA. The roles of host 5-methylcytosine RNA methyltransferases during viral infections.Int. J. Mol. Sci.20202121817610.3390/ijms2121817633142933
    [Google Scholar]
  34. NombelaP. Miguel-LópezB. BlancoS. The role of m6A, m5C and Ψ RNA modifications in cancer: Novel therapeutic opportunities.Mol. Cancer20212011810.1186/s12943‑020‑01263‑w33461542
    [Google Scholar]
  35. SchianoC. CostaV. AprileM. GrimaldiV. MaielloC. EspositoR. SoricelliA. ColantuoniV. DonatelliF. CiccodicolaA. NapoliC. Heart failure: Pilot transcriptomic analysis of cardiac tissue by RNA-sequencing.Cardiol. J.201724553955310.5603/CJ.a2017.005228497843
    [Google Scholar]
  36. LiX. XiongX. WangK. WangL. ShuX. MaS. YiC. Transcriptome-wide mapping reveals reversible and dynamic N1-methyladenosine methylome.Nat. Chem. Biol.201612531131610.1038/nchembio.204026863410
    [Google Scholar]
  37. MolinieB. WangJ. LimK.S. HillebrandR. LuZ. Van WittenbergheN. HowardB.D. DaneshvarK. MullenA.C. DedonP. XingY. GiallourakisC.C. m6A-LAIC-seq reveals the census and complexity of the m6A epitranscriptome.Nat. Methods201613869269810.1038/nmeth.389827376769
    [Google Scholar]
  38. DelatteB. WangF. NgocL.V. CollignonE. BonvinE. DeplusR. CalonneE. HassabiB. PutmansP. AweS. WetzelC. KreherJ. SoinR. CreppeC. LimbachP.A. GueydanC. KruysV. BrehmA. MinakhinaS. DefranceM. StewardR. FuksF. Transcriptome-wide distribution and function of RNA hydroxymethylcytosine.Science2016351627028228510.1126/science.aac525326816380
    [Google Scholar]
  39. GallowayA. KaskarA. DitsovaD. AtrihA. YoshikawaH. Gomez-MoreiraC. SuskaO. WarminskiM. GrzelaR. LamondA.I. DarzynkiewiczE. JemielityJ. CowlingV.H. Upregulation of RNA cap methyltransferase RNMT drives ribosome biogenesis during T cell activation.Nucleic Acids Res.202149126722673810.1093/nar/gkab46534125914
    [Google Scholar]
  40. DestefanisE. AvşarG. GrozaP. RomitelliA. TorriniS. PirP. ConticelloS.G. AguiloF. DassiE. A mark of disease: How mRNA modifications shape genetic and acquired pathologies.RNA202127436738910.1261/rna.077271.12033376192
    [Google Scholar]
  41. KudoI. LeineweberM. RajBhandaryU.L. Site-specific mutagenesis on cloned DNAs: generation of a mutant of Escherichia coli tyrosine suppressor tRNA in which the sequence G-T-T-C corresponding to the universal G-T-pseudouracil-C sequence of tRNAs is changed to G-A-T-C.Proc. Natl. Acad. Sci. USA19817884753475710.1073/pnas.78.8.47536170979
    [Google Scholar]
  42. HuP. DharmayatK.I. StevensC.A.T. SharabianiM.T.A. JonesR.S. WattsG.F. GenestJ. RayK.K. Vallejo-VazA.J. Prevalence of familial hypercholesterolemia among the general population and patients with atherosclerotic cardiovascular disease.Circulation2020141221742175910.1161/CIRCULATIONAHA.119.04479532468833
    [Google Scholar]
  43. ArnettD.K. BlumenthalR.S. AlbertM.A. BurokerA.B. GoldbergerZ.D. HahnE.J. HimmelfarbC.D. KheraA. Lloyd-JonesD. McEvoyJ.W. MichosE.D. MiedemaM.D. MuñozD. SmithS.C.Jr ViraniS.S. WilliamsK.A.Sr YeboahJ. ZiaeianB. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: A report of the american college of cardiology/american heart association task force on clinical practice guidelines.Circulation201914011e596e64610.1161/CIR.000000000000067830879355
    [Google Scholar]
  44. NapoliC. BenincasaG. SchianoC. SalvatoreM. Differential epigenetic factors in the prediction of cardiovascular risk in diabetic patients.Eur. Heart J. Cardiovasc. Pharmacother.20206423924710.1093/ehjcvp/pvz06231665258
    [Google Scholar]
  45. SchianoC. BalbiC. BurrelloJ. RuoccoA. InfanteT. FioritoC. PanellaS. BarileL. MauroC. VassalliG. NapoliC. De novo DNA methylation induced by circulating extracellular vesicles from acute coronary syndrome patients.Atherosclerosis2022354415210.1016/j.atherosclerosis.2022.06.102635830762
    [Google Scholar]
  46. SchianoC. BalbiC. de NigrisF. NapoliC. Basic pathogenic mechanisms and epigenetic players promoted by extracellular vesicles in vascular damage.Int. J. Mol. Sci.2023248750910.3390/ijms2408750937108672
    [Google Scholar]
  47. SchianoC. BenincasaG. FranzeseM. Della MuraN. PaneK. SalvatoreM. NapoliC. Epigenetic-sensitive pathways in personalized therapy of major cardiovascular diseases.Pharmacol. Ther.202021010751410.1016/j.pharmthera.2020.10751432105674
    [Google Scholar]
  48. LiuC. GuL. DengW. MengQ. LiN. DaiG. YuS. FangH. N6-methyladenosine RNA methylation in cardiovascular diseases.Front. Cardiovasc. Med.2022988783810.3389/fcvm.2022.88783835571209
    [Google Scholar]
  49. MilutinovićA ŠuputD Zorc-PleskovičR. Pathogenesis of atherosclerosis in the tunica intima, media, and adventitia of coronary arteries: An updated review.Bosn. J. Basic Med. Sci.202020213010.17305/bjbms.2019.4320
    [Google Scholar]
  50. ChenLH ZhaoYY HuangL LiYZ XuHQ YangC ZhangC. The potential roles of RNA N6-methyladenosine in atherosclerosis.Eur. Rev. Med. Pharmacol. Sci.20222610751083
    [Google Scholar]
  51. XuZ QiuP JiangY HuJ WuZ LeiJ PuH HuangQ WangX LiB YeK LuX LiuG. m6A modification mediates endothelial cell responses to oxidative stress in vascular aging induced by low fluid shear stress.Oxid. Med. Cell Longev.2023813402710.3389/fcvm.2022.913039
    [Google Scholar]
  52. ZhaoY XiaA LiC LongX BaiZ QiuZ XiongW GuN ShenY ZhaoR ShiB. Methyltransferase like 3-mediated N6-methylatidin methylation inhibits vascular smooth muscle cells phenotype switching via promoting phosphatidylinositol 3-kinase mRNA decay.Front Cardiovasc Med20229913039
    [Google Scholar]
  53. ZhuB. GongY. ShenL. LiJ. HanJ. SongB. HuL. WangQ. WangZ. Total Panax notoginseng saponin inhibits vascular smooth muscle cell proliferation and migration and intimal hyperplasia by regulating WTAP/p16 signals via m6A modulation.Biomed. Pharmacother.202012410993510.1016/j.biopha.2020.10993531986407
    [Google Scholar]
  54. HuoY.B. GaoX. PengQ. NieQ. BiW. Dihydroartemisinin alleviates AngII-induced vascular smooth muscle cell proliferation and inflammatory response by blocking the FTO/NR4A3 axis.Inflamm. Res.202271224325310.1007/s00011‑021‑01533‑335059772
    [Google Scholar]
  55. DengK. NingX. RenX. YangB. LiJ. CaoJ. ChenJ. LuX. ChenS. WangL. Transcriptome-wide N6-methyladenosine methylation landscape of coronary artery disease.Epigenomics2021131079380810.2217/epi‑2020‑037233876670
    [Google Scholar]
  56. YuanJ. LiuY. ZhouL. XueY. LuZ. GanJ. YTHDC2-mediated circYTHDC2 N6-methyladenosine modification promotes vascular smooth muscle cells dysfunction through inhibiting ten-eleven translocation 2.Front. Cardiovasc. Med.2021868629310.3389/fcvm.2021.68629334660707
    [Google Scholar]
  57. ZhangB. WuZ. DengJ. JinH. ChenW. ZhangS. LiuX. WangW. ZhengX. M6A methylation-mediated elevation of SM22α inhibits the proliferation and migration of vascular smooth muscle cells and ameliorates intimal hyperplasia in type 2 diabetes mellitus.Biol. Chem.2022403331732910.1515/hsz‑2021‑029634882999
    [Google Scholar]
  58. HanD. ZhouT. LiL. MaY. ChenS. YangC. MaN. SongM. ZhangS. WuJ. CaoF. WangY. AVCAPIR: A novel procalcific piwi-interacting RNA in calcific aortic valve disease.Circulation2024149201578159710.1161/CIRCULATIONAHA.123.06521338258575
    [Google Scholar]
  59. NossentA.Y. The epitranscriptome: RNA modifications in vascular remodelling.Atherosclerosis2023374243310.1016/j.atherosclerosis.2022.11.00436400603
    [Google Scholar]
  60. YuanS TangH XingJ FanX CaiX LiQ HanP LuoY ZhangZ JiangB DouY GorospeM WangW Methylation by NSun2 represses the levels and function of microRNA 125b.Mol Cell Biol2014343630364110.1128/MCB.00243‑14
    [Google Scholar]
  61. YinL ZhuX NovákP ZhouL GaoL YangM ZhaoG YinK. The epitranscriptome of long noncoding RNAs in metabolic diseases.Clin Chim Acta2021515808910.1016/j.cca.2021.01.001
    [Google Scholar]
  62. InfanteT. Del ViscovoL. De RiminiM.L. PadulaS. CasoP. NapoliC. Network medicine: A clinical approach for precision medicine and personalized therapy in coronary heart disease.J. Atheroscler. Thromb.202027427930210.5551/jat.5240731723086
    [Google Scholar]
  63. de NigrisF. CacciatoreF. ManciniF.P. VitaleD.F. MansuetoG. D’ArmientoF.P. SchianoC. SoricelliA. NapoliC. Epigenetic hallmarks of fetal early atherosclerotic lesions in humans.JAMA Cardiol.20183121184119110.1001/jamacardio.2018.354630419118
    [Google Scholar]
  64. LiZ. XuQ. HuangfuN. ChenX. ZhuJ. Mettl3 promotes oxLDL-mediated inflammation through activating STAT1 signaling.J. Clin. Lab. Anal.2022361e2401910.1002/jcla.2401934825733
    [Google Scholar]
  65. HuangfuN. ZhengW. XuZ. WangS. WangY. ChengJ. LiZ. ChengK. ZhangS. ChenX. ZhuJ. RBM4 regulates M1 macrophages polarization through targeting STAT1-mediated glycolysis.Int. Immunopharmacol.20208310643210.1016/j.intimp.2020.10643232248017
    [Google Scholar]
  66. GuX. ZhangY. LiD. CaiH. CaiL. XuQ. N6-methyladenosine demethylase FTO promotes M1 and M2 macrophage activation.Cell. Signal.20206910955310.1016/j.cellsig.2020.10955332018056
    [Google Scholar]
  67. ChienC.S. LiJ.Y.S. ChienY. WangM.L. YarmishynA.A. TsaiP.H. JuanC.C. NguyenP. ChengH. HuoT.I. ChiouS.H. ChienS. METTL3-dependent N6-methyladenosine RNA modification mediates the atherogenic inflammatory cascades in vascular endothelium.Proc. Natl. Acad. Sci. USA20211187e202507011810.1073/pnas.202507011833579825
    [Google Scholar]
  68. YuR. LiQ. FengZ. CaiL. XuQ. m6A reader YTHDF2 regulates LPS-induced inflammatory response.Int. J. Mol. Sci.2019206132310.3390/ijms2006132330875984
    [Google Scholar]
  69. SunZ. ChenW. WangZ. WangS. ZanJ. ZhengL. ZhaoW. Matr3 reshapes m6A modification complex to alleviate macrophage inflammation during atherosclerosis.Clin. Immunol.202224510917610.1016/j.clim.2022.10917636368640
    [Google Scholar]
  70. ZhongX. YuJ. FrazierK. WengX. LiY. ChamC.M. DolanK. ZhuX. HubertN. TaoY. LinF. Martinez-GurynK. HuangY. WangT. LiuJ. HeC. ChangE.B. LeoneV. Circadian clock regulation of hepatic lipid metabolism by modulation of m6A mRNA methylation.Cell Rep.201825718161828.e410.1016/j.celrep.2018.10.06830428350
    [Google Scholar]
  71. ZhaoW. WangZ. SunZ. HeY. JianD. HuX. ZhangW. ZhengL. RNA helicase DDX5 participates in oxLDL-induced macrophage scavenger receptor 1 expression by suppressing mRNA degradation.Exp. Cell Res.2018366211412010.1016/j.yexcr.2018.03.00329522752
    [Google Scholar]
  72. KangH. ZhangZ. YuL. LiY. LiangM. ZhouL. FTO reduces mitochondria and promotes hepatic fat accumulation through RNA demethylation.J. Cell. Biochem.201811975676568510.1002/jcb.2674629384213
    [Google Scholar]
  73. MoX.B. LeiS.F. ZhangY.H. ZhangH. Examination of the associations between m6A-associated single-nucleotide polymorphisms and blood pressure.Hypertens. Res.201942101582158910.1038/s41440‑019‑0277‑831175347
    [Google Scholar]
  74. MoX.B. LeiS.F. ZhangY.H. ZhangH. Integrative analysis identified IRF6 and NDST1 as potential causal genes for ischemic stroke.Front. Neurol.20191051710.3389/fneur.2019.0051731156544
    [Google Scholar]
  75. BenincasaG. de CandiaP. CostaD. FaenzaM. MansuetoG. AmbrosioG. NapoliC. Network medicine approach in prevention and personalized treatment of dyslipidemias.Lipids202156325926810.1002/lipd.1229033118184
    [Google Scholar]
  76. WuQ. YuanX. HanR. ZhangH. XiuR. Epitranscriptomic mechanisms of N6-methyladenosine methylation regulating mammalian hypertension development by determined spontaneously hypertensive rats pericytes.Epigenomics201911121359137010.2217/epi‑2019‑014831357869
    [Google Scholar]
  77. GuoY. PeiY. LiK. CuiW. ZhangD. DNA N6-methyladenine modification in hypertension.Aging20201276276629110.18632/aging.10302332283543
    [Google Scholar]
  78. MarcadentiA. FuchsF.D. MatteU. SperbF. MoreiraL.B. FuchsS.C. Effects of FTO RS9939906 and MC4R RS17782313 on obesity, type 2 diabetes mellitus and blood pressure in patients with hypertension.Cardiovasc. Diabetol.201312110310.1186/1475‑2840‑12‑10323849767
    [Google Scholar]
  79. ÄijäläM. RonkainenJ. HuuskoT. MaloE. SavolainenE.R. SavolainenM.J. SalonurmiT. BloiguR. Antero KesäniemiY. UkkolaO. The fat mass and obesity-associated (FTO) gene variant rs9939609 predicts long-term incidence of cardiovascular disease and related death independent of the traditional risk factors.Ann. Med.201547865566310.3109/07853890.2015.109108826555680
    [Google Scholar]
  80. QiuL. JingQ. LiY. HanJ. RNA modification: Mechanisms and therapeutic targets.Molecular Biomedicine2023412510.1186/s43556‑023‑00139‑x37612540
    [Google Scholar]
  81. De JesusD.F. ZhangZ. KahramanS. BrownN.K. ChenM. HuJ. GuptaM.K. HeC. KulkarniR.N. m6A mRNA methylation regulates human β-cell biology in physiological states and in type 2 diabetes.Nat. Metab.20191876577410.1038/s42255‑019‑0089‑931867565
    [Google Scholar]
  82. CullyM. Chemical inhibitors make their RNA epigenetic mark.Nat. Rev. Drug Discov.2019181289289410.1038/d41573‑019‑00179‑531780844
    [Google Scholar]
  83. EsteyE.H. Epigenetics in clinical practice: The examples of azacitidine and decitabine in myelodysplasia and acute myeloid leukemia.Leukemia20132791803181210.1038/leu.2013.17323757301
    [Google Scholar]
  84. NicorescuI. DallingaG.M. de WintherM.P.J. StroesE.S.G. BahjatM. Potential epigenetic therapeutics for atherosclerosis treatment.Atherosclerosis201928118919710.1016/j.atherosclerosis.2018.10.00630340764
    [Google Scholar]
  85. ZhouL.L. XuH. HuangY. YangC.G. Targeting the RNA demethylase FTO for cancer therapy.RSC Chemical Biology2021251352136910.1039/D1CB00075F34704042
    [Google Scholar]
  86. HanZ. NiuT. ChangJ. LeiX. ZhaoM. WangQ. ChengW. WangJ. FengY. ChaiJ. Crystal structure of the FTO protein reveals basis for its substrate specificity.Nature201046472921205120910.1038/nature0892120376003
    [Google Scholar]
  87. StellosK. GatsiouA. StamatelopoulosK. Perisic MaticL. JohnD. LunellaF.F. JaéN. RossbachO. AmrheinC. SigalaF. BoonR.A. FürtigB. ManavskiY. YouX. UchidaS. KellerT. BoeckelJ.N. Franco-CerecedaA. MaegdefesselL. ChenW. SchwalbeH. BindereifA. ErikssonP. HedinU. ZeiherA.M. DimmelerS. Adenosine-to-inosine RNA editing controls cathepsin S expression in atherosclerosis by enabling HuR-mediated post-transcriptional regulation.Nat. Med.201622101140115010.1038/nm.417227595325
    [Google Scholar]
  88. MathiyalaganP. AdamiakM. MayourianJ. SassiY. LiangY. AgarwalN. JhaD. ZhangS. KohlbrennerE. ChepurkoE. ChenJ. TrivieriM.G. SinghR. BoucharebR. FishK. IshikawaK. LebecheD. HajjarR.J. SahooS. FTO-dependent N6-methyladenosine regulates cardiac function during remodeling and repair.Circulation2019139451853210.1161/CIRCULATIONAHA.118.03379429997116
    [Google Scholar]
  89. XuS.S. DingJ.F. ShiP. ShiK.H. TaoH. DNMT1-induced miR-152-3p suppression facilitates cardiac fibroblast activation in cardiac fibrosis.Cardiovasc. Toxicol.2021211298499910.1007/s12012‑021‑09690‑x34424481
    [Google Scholar]
  90. ZhuangY. LiT. HuX. XieY. PeiX. WangC. LiY. LiuJ. TianZ. ZhangX. PengL. MengB. WuH. YuanW. PanZ. LuY. MetBil as a novel molecular regulator in ischemia-induced cardiac fibrosis via METTL3 -mediated m6A modification.FASEB J.2023373e2279710.1096/fj.202201734R36753405
    [Google Scholar]
  91. SiW. LiY. YeS. LiZ. LiuY. KuangW. ChenD. ZhuM. Methyltransferase 3 mediated miRNA m6A methylation promotes stress granule formation in the early stage of acute ischemic stroke.Front. Mol. Neurosci.20201310310.3389/fnmol.2020.0010332581712
    [Google Scholar]
  92. ChokkallaA.K. PajdzikK. DouX. DaiQ. MehtaS.L. ArruriV. VemugantiR. Dysregulation of the epitranscriptomic mark m1A in ischemic stroke.Transl. Stroke Res.202314680681010.1007/s12975‑022‑01056‑x35737185
    [Google Scholar]
  93. HeY. XingJ. WangS. XinS. HanY. ZhangJ. Increased m6A methylation level is associated with the progression of human abdominal aortic aneurysm.Ann. Transl. Med.201972479710.21037/atm.2019.12.6532042813
    [Google Scholar]
  94. ZhangB.Y. HanL. TangY.F. ZhangG.X. FanX.L. ZhangJ.J. XueQ. XuZ.Y. METTL14 regulates M6A methylation-modified primary miR-19a to promote cardiovascular endothelial cell proliferation and invasion.Eur. Rev. Med. Pharmacol. Sci.202024127015702310.26355/eurrev_202006_2169432633395
    [Google Scholar]
  95. HeY. ZhangH. YinF. GuoP. WangS. WuY. XinS. HanY. ZhangJ. Novel insights into the role of 5-Methylcytosine RNA methylation in human abdominal aortic aneurysm.Front. Biosci.-Landmark202126111147116510.52586/501634856760
    [Google Scholar]
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