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Volume 26, Issue 1
  • ISSN: 1389-2010
  • E-ISSN: 1873-4316

Abstract

Pulmonary Hypertension (PH) is a complex cardiovascular disorder characterized by elevated blood pressure in the pulmonary arteries. Current therapeutic approaches for PH have limitations in addressing the underlying molecular mechanisms. This article explores the potential of noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), delivered through Lipid-Based Nanoparticles (LNPs) as a novel treatment strategy. These ncRNAs play critical roles in regulating vascular function and are implicated in PH pathogenesis. LNPs provide a promising method for the efficient and targeted delivery of ncRNAs. Advances in LNP technology, including the incorporation of R8 peptide modification, have shown promise in enhancing the delivery and efficacy of ncRNAs in PH models. Challenges such as biocompatibility, toxicity, and precise targeting must be addressed as these therapies move toward clinical application. The potential of personalized medicine and the integration of artificial intelligence in LNP design are discussed as prospects. In conclusion, ncRNA lipotherapeutics delivered LNPs offer a transformative approach to treating PH, potentially leading to more effective management and improved patient outcomes in the future. However, continued research and clinical trials are necessary to fully realize their therapeutic potential in the field of PH treatment.

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2024-03-29
2024-12-28

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References

  1. GelzinisT.A. Pulmonary hypertension in 2021: Part I—Definition, classification, pathophysiology, and presentation.J. Cardiothorac. Vasc. Anesth.20223661552156410.1053/j.jvca.2021.06.036 34344595
     [Google Scholar]
  2. MaronB.A. Revised definition of pulmonary hypertension and approach to management: A clinical primer.J. Am. Heart Assoc.2023128e02902410.1161/JAHA.122.029024 37026538
     [Google Scholar]
  3. HuberL.C. ByeH. BrockM. The pathogenesis of pulmonary hypertension – An update.Swiss Med. Wkly.2015145w1420210.4414/smw.2015.14202 26479975
     [Google Scholar]
  4. BisserierM. PradhanN. HadriL. Current and emerging therapeutic approaches to pulmonary hypertension.Rev. Cardiovasc. Med.202021216317910.31083/j.rcm.2020.02.597 32706206
     [Google Scholar]
  5. JohnsonS. SommerN. Cox-FlahertyK. WeissmannN. VentetuoloC.E. MaronB.A. Pulmonary hypertension: A contemporary review.Am. J. Respir. Crit. Care Med.2023208552854810.1164/rccm.202302‑0327SO 37450768
     [Google Scholar]
  6. AmbrosV. The functions of animal microRNAs.Nature2004431700635035510.1038/nature02871 15372042
     [Google Scholar]
  7. ContiI. VaranoG. SimioniC. LafaceI. MilaniD. RimondiE. NeriL.M. miRNAs as influencers of cell–cell communication in tumor microenvironment.Cells20209122010.3390/cells9010220 31952362
     [Google Scholar]
  8. MatsuyamaH. SuzukiH.I. Systems and synthetic microRNA biology: From biogenesis to disease pathogenesis.Int. J. Mol. Sci.201921113210.3390/ijms21010132 31878193
     [Google Scholar]
  9. HermanA.B. TsitsipatisD. GorospeM. Integrated lncRNA function upon genomic and epigenomic regulation.Mol. Cell202282122252226610.1016/j.molcel.2022.05.027 35714586
     [Google Scholar]
  10. VollmersA. CarpenterS. Introduction and overview.Adv. Exp. Med. Biol.202213633810.1007/978‑3‑030‑92034‑0_1 35220562
     [Google Scholar]
  11. ChenL.L. The expanding regulatory mechanisms and cellular functions of circular RNAs.Nat. Rev. Mol. Cell Biol.202021847549010.1038/s41580‑020‑0243‑y 32366901
     [Google Scholar]
  12. VerduciL. TarcitanoE. StranoS. YardenY. BlandinoG. CircRNAs: Role in human diseases and potential use as biomarkers.Cell Death Dis.202112546810.1038/s41419‑021‑03743‑3 33976116
     [Google Scholar]
  13. XuJ. LinnemanJ. ZhongY. YinH. XiaQ. KangK. GouD. MicroRNAs in pulmonary hypertension, from pathogenesis to diagnosis and treatment.Biomolecules202212449610.3390/biom12040496 35454085
     [Google Scholar]
  14. AliM.K. SchimmelK. ZhaoL. ChenC.K. DuaK. NicollsM.R. SpiekerkoetterE. The role of circular RNAs in pulmonary hypertension.Eur. Respir. J.2022606220001210.1183/13993003.00012‑2022 35680145
     [Google Scholar]
  15. NapoliC. BenincasaG. LoscalzoJ. Epigenetic inheritance underlying pulmonary arterial hypertension.Arterioscler. Thromb. Vasc. Biol.201939465366410.1161/ATVBAHA.118.312262 30727752
     [Google Scholar]
  16. HuesoM. MallénA. PouS.M. AranJ.M. NegreS.J.M. NavarroE. ncRNAs in therapeutics: Challenges and limitations in nucleic acid-based drug delivery.Int. J. Mol. Sci.202122211159610.3390/ijms222111596 34769025
     [Google Scholar]
  17. JiaY. WangX. LiL. LiF. ZhangJ. LiangX.J. Lipid nanoparticles optimized for targeting and release of nucleic acid.Adv. Mater.2024364230530010.1002/adma.202305300 37547955
     [Google Scholar]
  18. YangL. GongL. WangP. ZhaoX. ZhaoF. ZhangZ. LiY. HuangW. Recent advances in lipid nanoparticles for delivery of mRNA.Pharmaceutics20221412268210.3390/pharmaceutics14122682 36559175
     [Google Scholar]
  19. NakamuraK. AkagiS. EjiriK. YoshidaM. MiyoshiT. TohN. NakagawaK. TakayaY. MatsubaraH. ItoH. Current treatment strategies and nanoparticle-mediated drug delivery systems for pulmonary arterial hypertension.Int. J. Mol. Sci.20192023588510.3390/ijms20235885 31771203
     [Google Scholar]
  20. ShahA.M. GiaccaM. Small non-coding RNA therapeutics for cardiovascular disease.Eur. Heart J.202243434548456110.1093/eurheartj/ehac463 36106499
     [Google Scholar]
  21. PaunovskaK. LoughreyD. DahlmanJ.E. Drug delivery systems for RNA therapeutics.Nat. Rev. Genet.202223526528010.1038/s41576‑021‑00439‑4 34983972
     [Google Scholar]
  22. AlzhraniR. AlsaabH.O. PetroviciA. BhiseK. VanamalaK. SauS. KrinockM.J. IyerA.K. Improving the therapeutic efficiency of noncoding RNAs in cancers using targeted drug delivery systems.Drug Discov. Today202025471873010.1016/j.drudis.2019.11.006 31758914
     [Google Scholar]
  23. JungH.N. LeeS.Y. LeeS. YounH. ImH.J. Lipid nanoparticles for delivery of RNA therapeutics: Current status and the role of in vivo imaging.Theranostics202212177509753110.7150/thno.77259 36438494
     [Google Scholar]
  24. WangX. LiuS. SunY. YuX. LeeS.M. ChengQ. WeiT. GongJ. RobinsonJ. ZhangD. LianX. BasakP. SiegwartD.J. Preparation of selective organ-targeting (SORT) lipid nanoparticles (LNPs) using multiple technical methods for tissue-specific mRNA delivery.Nat. Protoc.202318126529110.1038/s41596‑022‑00755‑x 36316378
     [Google Scholar]
  25. QiuM. TangY. ChenJ. MuriphR. YeZ. HuangC. EvansJ. HenskeE.P. XuQ. Lung-selective mRNA delivery of synthetic lipid nanoparticles for the treatment of pulmonary lymphangioleiomyomatosis.Proc. Natl. Acad. Sci. USA20221198e211627111910.1073/pnas.2116271119 35173043
     [Google Scholar]
  26. KimM. JeongM. LeeG. LeeY. ParkJ. JungH. ImS. YangJ.S. KimK. LeeH. Novel piperazine‐based ionizable lipid nanoparticles allow the repeated dose of mRNA to fibrotic lungs with improved potency and safety.Bioeng. Transl. Med.202386e1055610.1002/btm2.10556 38023699
     [Google Scholar]
  27. ZhangY. SunC. WangC. JankovicK.E. DongY. Lipids and lipid derivatives for RNA delivery.Chem. Rev.202112120121811227710.1021/acs.chemrev.1c00244 34279087
     [Google Scholar]
  28. ChenZ. TianY. YangJ. WuF. LiuS. CaoW. XuW. HuT. SiegwartD.J. XiongH. Modular design of biodegradable ionizable lipids for improved mRNA delivery and precise cancer metastasis delineation in vivo.J. Am. Chem. Soc.202314544243022431410.1021/jacs.3c09143 37853662
     [Google Scholar]
  29. VlatkovicI. Non-immunotherapy application of LNP-mRNA: Maximizing efficacy and safety.Biomedicines20219553010.3390/biomedicines9050530 34068715
     [Google Scholar]
  30. CullisP.R. HopeM.J. Lipid nanoparticle systems for enabling gene therapies.Mol. Ther.20172571467147510.1016/j.ymthe.2017.03.013 28412170
     [Google Scholar]
  31. GiannottaG. GiannottaN. mRNA COVID-19 vaccines and long-lived plasma cells: A complicated relationship.Vaccines2021912150310.3390/vaccines9121503 34960249
     [Google Scholar]
  32. CalinaD. HernándezA.F. HartungT. EgorovA.M. IzotovB.N. NikolouzakisT.K. TsatsakisA. VlachoyiannopoulosP.G. DoceaA.O. Challenges and scientific prospects of the newest generation of mrna-based vaccines against SARS-CoV-2.Life202111990710.3390/life11090907 34575056
     [Google Scholar]
  33. NgJ.Y. Inadvertent subcutaneous injection of COVID-19 vaccine.Postgrad. Med. J.202197114840010.1136/postgradmedj‑2021‑139870 33589486
     [Google Scholar]
  34. DiJ. DuZ. WuK. JinS. WangX. LiT. XuY. Biodistribution and non-linear gene expression of mRNA LNPs affected by delivery route and particle size.Pharm. Res.202239110511410.1007/s11095‑022‑03166‑5 35080707
     [Google Scholar]
  35. LokugamageM.P. VanoverD. BeyersdorfJ. HatitM.Z.C. RotoloL. EcheverriE.S. PeckH.E. NiH. YoonJ.K. KimY. SantangeloP.J. DahlmanJ.E. Optimization of lipid nanoparticles for the delivery of nebulized therapeutic mRNA to the lungs.Nat. Biomed. Eng.2021591059106810.1038/s41551‑021‑00786‑x 34616046
     [Google Scholar]
  36. CardarelliF. DigiacomoL. MarchiniC. AmiciA. SalomoneF. FiumeG. RossettaA. GrattonE. PozziD. CaraccioloG. The intracellular trafficking mechanism of Lipofectamine-based transfection reagents and its implication for gene delivery.Sci. Rep.2016612587910.1038/srep25879 27165510
     [Google Scholar]
  37. McLendonJ.M. JoshiS.R. SparksJ. MatarM. FewellJ.G. AbeK. OkaM. McMurtryI.F. GerthofferW.T. Lipid nanoparticle delivery of a microRNA-145 inhibitor improves experimental pulmonary hypertension.J. Control. Release2015210677510.1016/j.jconrel.2015.05.261 25979327
     [Google Scholar]
  38. RussomannoG. JoK.B. Abdul-SalamV.B. MorganC. EndruschatJ. SchaeperU. OsmanA.H. AlzaydiM.M. WilkinsM.R. StothardW.B. miR-150-PTPMT1-cardiolipin signaling in pulmonary arterial hypertension.Mol. Ther. Nucleic Acids20212314215310.1016/j.omtn.2020.10.042 33335799
     [Google Scholar]
  39. YinY. WuX. YangZ. ZhaoJ. WangX. ZhangQ. YuanM. XieL. LiuH. HeQ. The potential efficacy of R8-modified paclitaxel-loaded liposomes on pulmonary arterial hypertension.Pharm. Res.20133082050206210.1007/s11095‑013‑1058‑8 23756757
     [Google Scholar]
  40. XingY. ZhengX. FuY. QiJ. LiM. MaM. WangS. LiS. ZhuD. Long noncoding RNA-maternally expressed gene 3 contributes to hypoxic pulmonary hypertension.Mol. Ther.201927122166218110.1016/j.ymthe.2019.07.022 31477557
     [Google Scholar]
/content/journals/cpb/10.2174/0113892010302590240321073509
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Noncoding RNA Lipotherapeutics: A Promising Breakthrough in Pulmonary Hypertension Treatment
Current Pharmaceutical Biotechnology 26, 9 (2025); https://doi.org/10.2174/0113892010302590240321073509
/content/journals/cpb/10.2174/0113892010302590240321073509
/content/journals/cpb/10.2174/0113892010302590240321073509
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  • Article Type:     Review Article
Keyword(s): circRNAs; lipotherapeutics; lncRNAs; LNPs; miRNAs; ncRNA; pulmonary hypertension

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