Skip to content
2000
Volume 26, Issue 17
  • ISSN: 1389-2010
  • E-ISSN: 1873-4316

Abstract

Background

At present, the research on the potential molecular mechanism of abdominal aortic aneurysm (AAA) is limited, which hinders the treatment of aneurysm and the development of drugs. CircRNA has been identified as a potential therapeutic target for diagnostic biomarkers in a variety of diseases. The purpose of this study was to explore the molecular mechanism of circLRP6 in AAA and to provide a theoretical basis for further clinical optimization of treatment.

Methods

The animal model and cell model of AAA were constructed, and the circLRP6 expression was verified by in situ hybridization and qRT-PCR. The effect of circLRP6 on cell viability was determined using CCK-8 and BrdU. The effects of circLRP6 on the cell cycle and apoptosis were determined by flow cytometry. In addition, the interaction of circLRP6 with miR-29a-3p and HIF-1α was verified by the luciferase reporter gene and RIP. HIF-1α or caspase 3 expression was detected by immunofluorescence or western blot analysis.

Results

Our previous results showed that the circLRP6 had reduced expression in AAA, and its overexpression significantly inhibited AngII-induced hAoSMC cell viability. In addition, bioinformatics prediction showed that there was a binding site between miR-29a-3p and circLRP6, showing a negative regulatory relationship in hAoSMC. In addition, the results of the luciferase reporter gene and RIP showed that the circLRP6 interacted with HIF-1α, and achieved effective treatment of AAA by inhibiting the miR-29a-3p/HIF-1α.

Conclusion

CircLRP6 effectively inhibited the development of AAA by inhibiting the miR-29a-3p/HIF-1α, providing a theoretical basis for further clinical optimization of treatment.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cpb/10.2174/0113892010327133250424073216
2025-05-12
2026-02-26

  • From This Site

    /content/journals/cpb/10.2174/0113892010327133250424073216
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Tchana-SatoV. SakalihasanN. DefraigneJ.O. Ruptured abdominal aortic aneurysm.Rev. Med. Liege2018735-629629929926569
     [Google Scholar]
  2. ClancyK. WongJ. SpicherA. Abdominal aortic aneurysm: A case report and literature review.Perm. J.201923418.21810.7812/TPP/18.21831926569
     [Google Scholar]
  3. Schmitz-RixenT. KeeseM. HakimiM. PetersA. BöcklerD. NelsonK. GrundmannR.T. Ruptured abdominal aortic aneurysm—epidemiology, predisposing factors, and biology.Langenbecks Arch. Surg.2016401327528810.1007/s00423‑016‑1401‑827001684
     [Google Scholar]
  4. NguyenV.L. LeinerT. HellenthalF.A.M.V.I. BackesW.H. WishauptM.C.J. van der GeestR.J. HeenemanS. KooiM.E. SchurinkG.W.H. Abdominal aortic aneurysms with high thrombus signal intensity on magnetic resonance imaging are associated with high growth rate.Eur. J. Vasc. Endovasc. Surg.201448667668410.1016/j.ejvs.2014.04.02524935911
     [Google Scholar]
  5. WangY. LiuZ. RenJ. XiangM.X. Pharmacological therapy of abdominal aortic aneurysm: An update.Curr. Vasc. Pharmacol.201816211412410.2174/157016111566617041314570528412911
     [Google Scholar]
  6. AnagnostakosJ. LalB.K. Abdominal aortic aneurysms.Prog. Cardiovasc. Dis.202165344310.1016/j.pcad.2021.03.00933831398
     [Google Scholar]
  7. NemethK. BayraktarR. FerracinM. CalinG.A. Non-coding RNAs in disease: From mechanisms to therapeutics.Nat. Rev. Genet.202425321123210.1038/s41576‑023‑00662‑137968332
     [Google Scholar]
  8. SalzmanJ. Circular RNA expression: Its potential regulation and function.Trends Genet.201632530931610.1016/j.tig.2016.03.00227050930
     [Google Scholar]
  9. HsiaoK.Y. SunH.S. TsaiS.J. Circular RNA – New member of noncoding RNA with novel functions.Exp. Biol. Med. (Maywood)2017242111136114110.1177/153537021770897828485684
     [Google Scholar]
  10. QuS. YangX. LiX. WangJ. GaoY. ShangR. SunW. DouK. LiH. CircularR.N.A. Circular RNA: A new star of noncoding RNAs.Cancer Lett.2015365214114810.1016/j.canlet.2015.06.00326052092
     [Google Scholar]
  11. WangJ. SunH. ZhouY. HuangK. QueJ. PengY. WangJ. LinC. XueY. JiK. Circular RNA microarray expression profile in 3,4‐benzopyrene/angiotensin II‐induced abdominal aortic aneurysm in mice.J. Cell. Biochem.20191206104841049410.1002/jcb.2833330614051
     [Google Scholar]
  12. ZhouM. ShiZ. CaiL. LiX. DingY. XieT. FuW. Circular RNA expression profile and its potential regulative role in human abdominal aortic aneurysm.BMC Cardiovasc. Disord.20202017010.1186/s12872‑020‑01374‑832039711
     [Google Scholar]
  13. Di GregoliK. Mohamad AnuarN.N. BiancoR. WhiteS.J. NewbyA.C. GeorgeS.J. JohnsonJ.L. MicroRNA-181b controls atherosclerosis and aneurysms through regulation of TIMP-3 and elastin.Circ. Res.20171201496510.1161/CIRCRESAHA.116.30932127756793
     [Google Scholar]
  14. ZhengC. NiuH. LiM. ZhangH. YangZ. TianL. WuZ. LiD. ChenX. Cyclic RNA has-circ-000595 regulates apoptosis of aortic smooth muscle cells.Mol. Med. Rep.20151256656666210.3892/mmr.2015.426426324352
     [Google Scholar]
  15. QianG. AdeyanjuO. OlajuyinA. GuoX. Abdominal aortic aneurysm formation with a focus on vascular smooth muscle cells.Life (Basel)202212219110.3390/life1202019135207478
     [Google Scholar]
  16. QianH. YangY. LiJ. HuangJ. DouK. YangG. The role of vascular stem cells in atherogenesis and post-angioplasty restenosis.Ageing Res. Rev.20076210912710.1016/j.arr.2007.01.00117324640
     [Google Scholar]
  17. LuH. DuW. RenL. HamblinM.H. BeckerR.C. ChenY.E. FanY. Vascular smooth muscle cells in aortic aneurysm: From genetics to mechanisms.J. Am. Heart Assoc.20211024e02360110.1161/JAHA.121.02360134796717
     [Google Scholar]
  18. RomboutsK.B. van MerrienboerT.A.R. KetJ.C.F. BogunovicN. van der VeldenJ. YeungK.K. The role of vascular smooth muscle cells in the development of aortic aneurysms and dissections.Eur. J. Clin. Invest.2022524e1369710.1111/eci.1369734698377
     [Google Scholar]
  19. BaiY. LiuF. YangZ. CircRNA LRP6 promotes high-glucose induced proliferation and migration of vascular smooth muscle cells through regulating miR-545-3p/HMGA1 signaling axis.Am. J. Transl. Res.20211388909892034540004
     [Google Scholar]
  20. RouleauS. GlouzonJ.P.S. BrumwellA. BisaillonM. PerreaultJ.P. 3′ UTR G-quadruplexes regulate miRNA binding.RNA20172381172117910.1261/rna.060962.11728473452
     [Google Scholar]
  21. SunY. ZongC. LiuJ. ZengL. LiQ. LiuZ. LiY. ZhuJ. LiL. ZhangC. ZhangW. C-myc promotes miR-92a-2-5p transcription in rat ovarian granulosa cells after cadmium exposure.Toxicol. Appl. Pharmacol.202142111553610.1016/j.taap.2021.11553633865896
     [Google Scholar]
  22. KristensenL.S. AndersenM.S. StagstedL.V.W. EbbesenK.K. HansenT.B. KjemsJ. The biogenesis, biology and characterization of circular RNAs.Nat. Rev. Genet.2019201167569110.1038/s41576‑019‑0158‑731395983
     [Google Scholar]
  23. YueJ. ZhuT. YangJ. SiY. XuX. FangY. FuW. CircCBFB-mediated miR-28-5p facilitates abdominal aortic aneurysm via LYPD3 and GRIA4.Life Sci.202025311753310.1016/j.lfs.2020.11753332151690
     [Google Scholar]
  24. HallI.F. ClimentM. QuintavalleM. FarinaF.M. SchornT. ZaniS. CarulloP. KunderfrancoP. CiviliniE. CondorelliG. EliaL. Circ_Lrp6, a circular RNA enriched in vascular smooth muscle cells, acts as a sponge regulating miRNA-145 function.Circ. Res.2019124449851010.1161/CIRCRESAHA.118.31424030582454
     [Google Scholar]
  25. BoonR.A. SeegerT. HeydtS. FischerA. HergenreiderE. HorrevoetsA.J.G. VinciguerraM. RosenthalN. SciaccaS. PilatoM. van HeijningenP. EssersJ. BrandesR.P. ZeiherA.M. DimmelerS. MicroRNA-29 in aortic dilation: Implications for aneurysm formation.Circ. Res.2011109101115111910.1161/CIRCRESAHA.111.25573721903938
     [Google Scholar]
  26. MaegdefesselL. AzumaJ. TohR. MerkD.R. DengA. ChinJ.T. RaazU. SchoelmerichA.M. RaiesdanaA. LeeperN.J. McConnellM.V. DalmanR.L. SpinJ.M. TsaoP.S. Inhibition of microRNA-29b reduces murine abdominal aortic aneurysm development.J. Clin. Invest.2012122249750610.1172/JCI6159822269326
     [Google Scholar]
  27. KasivisvanathanV. ShalhoubJ. LimC.S. ShepherdA.C. ThaparA. DaviesA.H. Hypoxia-inducible factor-1 in arterial disease: A putative therapeutic target.Curr. Vasc. Pharmacol.20119333334910.2174/15701611179549560220807188
     [Google Scholar]
  28. BaoM.H. LiG.Y. HuangX.S. TangL. DongL.P. LiJ.M. Long noncoding RNA LINC00657 acting as a miR-590-3p sponge to facilitate low concentration oxidized low-density lipoprotein-induced angiogenesis.Mol. Pharmacol.201893436837510.1124/mol.117.11065029436491
     [Google Scholar]
  29. TsaiS.H. HuangP.H. HsuY.J. PengY.J. LeeC.H. WangJ.C. ChenJ.W. LinS.J. Inhibition of hypoxia inducible factor-1α attenuates abdominal aortic aneurysm progression through the down-regulation of matrix metalloproteinases.Sci. Rep.2016612861210.1038/srep2861227363580
     [Google Scholar]
  30. LimC.S. KiriakidisS. SandisonA. PaleologE.M. DaviesA.H. Hypoxia-inducible factor pathway and diseases of the vascular wall.J. Vasc. Surg.201358121923010.1016/j.jvs.2013.02.24023643279
     [Google Scholar]
  31. YangL. ShenL. LiG. YuanH. JinX. WuX. Silencing of hypoxia inducible factor-1α gene attenuated angiotensin II-induced abdominal aortic aneurysm in apolipoprotein E-deficient mice.Atherosclerosis2016252404910.1016/j.atherosclerosis.2016.07.01027497884
     [Google Scholar]
  32. WangW. XuB. XuanH. GeY. WangY. WangL. HuangJ. FuW. MichieS.A. DalmanR.L. Hypoxia-inducible factor 1 in clinical and experimental aortic aneurysm disease.J. Vasc. Surg.20186815381550
     [Google Scholar]
  33. BruhnP.J. JessenM.L. EibergJ. GhulamQ. HIF-1α in the pathogenesis of abdominal aortic aneurysms in vivo: A narrative review.JVS Vasc. Sci.2023510018910.1016/j.jvssci.2023.10018938379781
     [Google Scholar]
  34. LiD.Y. BuschA. JinH. ChernogubovaE. PelisekJ. KarlssonJ. SennbladB. LiuS. LaoS. HofmannP. BäcklundA. EkenS.M. RoyJ. ErikssonP. DackenB. RamanujamD. DueckA. EngelhardtS. BoonR.A. EcksteinH.H. SpinJ.M. TsaoP.S. MaegdefesselL. H19 induces abdominal aortic aneurysm development and progression.Circulation2018138151551156810.1161/CIRCULATIONAHA.117.03218429669788
     [Google Scholar]
  35. HeX. WangS. LiM. ZhongL. ZhengH. SunY. LaiY. ChenX. WeiG. SiX. HanY. HuangS. LiX. LiaoW. LiaoY. BinJ. Long noncoding RNA GAS5 induces abdominal aortic aneurysm formation by promoting smooth muscle apoptosis.Theranostics20199195558557610.7150/thno.3446331534503
     [Google Scholar]
  36. LiuS. ZhouH. HanD. SongH. LiY. HeS. DuY. WangK. HuangX. LiX. HuangZ. LncRNA CARMN inhibits abdominal aortic aneurysm formation and vascular smooth muscle cell phenotypic transformation by interacting with SRF.Cell. Mol. Life Sci.202481117510.1007/s00018‑024‑05193‑438597937
     [Google Scholar]
  37. LiH. ZhangH. WangG. ChenZ. PanY. LncRNA LBX2-AS1 facilitates abdominal aortic aneurysm through miR-4685-5p/LBX2 feedback loop.Biomed. Pharmacother.202012910990410.1016/j.biopha.2020.10990432559617
     [Google Scholar]
  38. HuM. YuanX. LiuY. TangS. MiaoJ. ZhouQ. ChenS. IL-1β-induced NF-κB activation down-regulates miR-506 expression to promotes osteosarcoma cell growth through JAG1.Biomed. Pharmacother.2017951147115510.1016/j.biopha.2017.08.12028926924
     [Google Scholar]
  39. YangH. HeC. BiY. ZhuX. DengD. RanT. JiX. Synergistic effect of VEGF and SDF-1α in endothelial progenitor cells and vascular smooth muscle cells.Front. Pharmacol.20221391434710.3389/fphar.2022.91434735910392
     [Google Scholar]
  40. ChenS. ChenY. YuL. HuX. YTHDC1 inhibits cell proliferation and angiogenesis in cervical cancer by regulating m6A modification of SOCS4 mRNA.Mol. Cell. Toxicol.202420353354010.1007/s13273‑023‑00360‑3
     [Google Scholar]
  41. JiangC. XieN. SunT. MaW. ZhangB. LiW. Xanthohumol inhibits TGF-β1-induced cardiac fibroblasts activation via mediating PTEN/Akt/mTOR signaling pathway.Drug Des. Devel. Ther.2020145431543910.2147/DDDT.S28220633324040
     [Google Scholar]
  42. HeJ. FengX. LiuY. WangY. GeC. LiuS. JiangY. Graveoline attenuates D-GalN/LPS-induced acute liver injury via inhibition of JAK1/STAT3 signaling pathway.Biomed. Pharmacother.202417711716310.1016/j.biopha.2024.11716339018876
     [Google Scholar]
  43. ChenB. LiY. LiuY. XuZ. circLRP6 regulates high glucose‐induced proliferation, oxidative stress, ECM accumulation, and inflammation in mesangial cells.J. Cell. Physiol.201923411212492125910.1002/jcp.2873031087368
     [Google Scholar]
  44. WeldenJ.R. StammS. Pre-mRNA structures forming circular RNAs.Gene Regulatory Mechanisms2019186211-1219441031421281
     [Google Scholar]
  45. LiD. YangY. LiZ.Q. LiL.C. ZhuX.H. Circular RNAs.Chin. Med. J.2019132202457246410.1097/CM9.000000000000046531651510
     [Google Scholar]
  46. ChenX. ZhouM. YantL. HuangC. Circular RNA in disease: Basic properties and biomedical relevance.Wiley Interdiscip. Rev. RNA2022136e172310.1002/wrna.172335194939
     [Google Scholar]
  47. WuM. XunM. ChenY. Circular RNAs: Regulators of vascular smooth muscle cells in cardiovascular diseases.J. Mol. Med.2022100451953510.1007/s00109‑022‑02186‑335254452
     [Google Scholar]
  48. MisirS. WuN. YangB.B. Specific expression and functions of circular RNAs.Cell Death Differ.202229348149110.1038/s41418‑022‑00948‑735169296
     [Google Scholar]
  49. ChokeE. CockerillG.W. DawsonJ. ChungY.L. GriffithsJ. WilsonR.W. LoftusI.M. ThompsonM.M. Hypoxia at the site of abdominal aortic aneurysm rupture is not associated with increased lactate.Ann. N. Y. Acad. Sci.20061085130631010.1196/annals.1383.00517182947
     [Google Scholar]
  50. Van Vickle-ChavezS.J. TungW.S. AbsiT.S. EnnisT.L. MaoD. CobbJ.P. ThompsonR.W. Temporal changes in mouse aortic wall gene expression during the development of elastase-induced abdominal aortic aneurysms.J. Vasc. Surg.20064351010102010.1016/j.jvs.2006.01.00416678698
     [Google Scholar]
  51. YuanM. WangL. WangH. ChenY. GuanH. Research progress on the role of HIF-1α in atherosclerosis.Chin. J. Arterioscler.202331815820
     [Google Scholar]
  52. HeA.T. LiuJ. LiF. YangB.B. Targeting circular RNAs as a therapeutic approach: Current strategies and challenges.Signal Transduct. Target. Ther.20216118510.1038/s41392‑021‑00569‑534016945
     [Google Scholar]
/content/journals/cpb/10.2174/0113892010327133250424073216
Loading
Circ-LRP6 Inhibits the Development and Progression of AAA Via miR-29a-3p/HIF-1α Axis
Current Pharmaceutical Biotechnology 26, 2738 (2025); https://doi.org/10.2174/0113892010327133250424073216
/content/journals/cpb/10.2174/0113892010327133250424073216
/content/journals/cpb/10.2174/0113892010327133250424073216
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher’s website along with the published article.

file format download Download

  • Article Type:     Research Article
Keyword(s): abdominal aortic aneurysm; CircLRP6; CircRNA; HIF-1α; miR-29a-3p; progression

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test