Skip to content
2000
Volume 22, Issue 1
  • ISSN: 1875-6921
  • E-ISSN: 1875-6913

Abstract

This review delves into the potential of epigenetic modifications as therapeutic targets in the management of hypertension, a major cardiovascular risk factor. Epigenetic mechanisms, particularly DNA methylation, histone modifications, and microRNA (miRNA) activity, play pivotal roles in gene expression regulation that pertains to blood pressure control. These modifications can affect several pathways involved in vascular function, renal sodium handling, and sympathetic nervous system activity, which are critical in the development and progression of hypertension. Recent studies have suggested that epigenetic modifications could serve as both biomarkers for hypertension and targets for novel therapeutic approaches. This article reviews the current understanding of epigenetic influences on hypertension and discusses the potential of epigenetic modifications to serve as a basis for the development of new therapeutic strategies.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cppm/10.2174/0118756921349049250324173511
2025-01-01
2025-10-18

  • From This Site

    /content/journals/cppm/10.2174/0118756921349049250324173511
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. MillisR.M. Epigenetics and hypertension.Curr. Hypertens. Rep.2011131212810.1007/s11906‑010‑0173‑821125351
     [Google Scholar]
  2. FrisoS. CarvajalC.A. FardellaC.E. OlivieriO. Epigenetics and arterial hypertension: The challenge of emerging evidence.Transl. Res.2015165115416510.1016/j.trsl.2014.06.00725035152
     [Google Scholar]
  3. KimG.H. RyanJ.J. MarsboomG. ArcherS.L. Epigenetic mechanisms of pulmonary hypertension.Pulm. Circ.20111334735610.4103/2045‑8932.8730022140624
     [Google Scholar]
  4. LevyE. SpahisS. BigrasJ.L. DelvinE. BorysJ.M. The epigenetic machinery in vascular dysfunction and hypertension.Curr. Hypertens. Rep.20171965210.1007/s11906‑017‑0745‑y28540644
     [Google Scholar]
  5. WiseI. CharcharF. Epigenetic modifications in essential hypertension.Int. J. Mol. Sci.201617445110.3390/ijms1704045127023534
     [Google Scholar]
  6. LiangM. CowleyA.W.Jr MattsonD.L. KotchenT.A. LiuY. Epigenomics of hypertension.Semin. Nephrol.201333439239910.1016/j.semnephrol.2013.05.01124011581
     [Google Scholar]
  7. MarkelA.L. RedinaO.E. Epigenetic mechanisms of blood-pressure regulation.Mol. Biol.201852217218929695687
     [Google Scholar]
  8. ChengX. WangY. DuL. Epigenetic modulation in the initiation and progression of pulmonary hypertension.Hypertension201974473373910.1161/HYPERTENSIONAHA.119.1345831476913
     [Google Scholar]
  9. FrisoS. CarvajalC. PizzoloF. FardellaC. OlivieriO. Epigenetics and arterial hypertension.Translating Epigenetics to the Clinic.Academic Press201715918410.1016/B978‑0‑12‑800802‑7.00007‑1
     [Google Scholar]
  10. ArifM. SadayappanS. BeckerR.C. MartinL.J. UrbinaE.M. Epigenetic modification: A regulatory mechanism in essential hypertension.Hypertens. Res.20194281099111310.1038/s41440‑019‑0248‑030867575
     [Google Scholar]
  11. KellyT.K. De CarvalhoD.D. JonesP.A. Epigenetic modifications as therapeutic targets.Nat. Biotechnol.201028101069107810.1038/nbt.167820944599
     [Google Scholar]
  12. Martinez-MorenoJ.M. Fontecha-BarriusoM. Martín-SánchezD. Epigenetic modifiers as potential therapeutic targets in diabetic kidney disease.Int. J. Mol. Sci.20202111411310.3390/ijms2111411332526941
     [Google Scholar]
  13. BayoJ. FioreE.J. DomínguezL.M. A comprehensive study of epigenetic alterations in hepatocellular carcinoma identifies potential therapeutic targets.J. Hepatol.2019711789010.1016/j.jhep.2019.03.00730880225
     [Google Scholar]
  14. ClausR. LübbertM. Epigenetic targets in hematopoietic malignancies.Oncogene200322426489649610.1038/sj.onc.120681414528273
     [Google Scholar]
  15. TakedaY. DemuraM. YonedaT. TakedaY. Epigenetic regulation of the renin–angiotensin–aldosterone system in hypertension.Int. J. Mol. Sci.20242515809910.3390/ijms2515809939125667
     [Google Scholar]
  16. García-GiménezJ.L. Seco-CerveraM. TollefsbolT.O. Epigenetic biomarkers: Current strategies and future challenges for their use in the clinical laboratory.Crit. Rev. Clin. Lab. Sci.2017547-852955010.1080/10408363.2017.141052029226748
     [Google Scholar]
  17. LiC. WangZ. WangL. ZhangC. Biosensors for epigenetic biomarkers detection: A review.Biosens. Bioelectron.201914411169510.1016/j.bios.2019.11169531526982
     [Google Scholar]
  18. LuoH. LiY. SongH. Role of EZH2-mediated epigenetic modification on vascular smooth muscle in cardiovascular diseases: A mini-review.Front. Pharmacol.202415141699210.3389/fphar.2024.141699238994197
     [Google Scholar]
  19. PandeyK.N. Genetic and epigenetic mechanisms regulating blood pressure and kidney dysfunction.Hypertension20248171424143710.1161/HYPERTENSIONAHA.124.2207238545780
     [Google Scholar]
  20. YaacoubS. BoudakaA. AlKhatibA. The pharmaco-epigenetics of hypertension: A focus on microRNA.Mol. Cell. Biochem.2024479123255327110.1007/s11010‑024‑04947‑938424404
     [Google Scholar]
  21. KumarP. Adams-SherrodG. BrooksH.L. Sex and age differentially regulate epigenetic modifications and renal injury markers in mice.Physiology202439S178410.1152/physiol.2024.39.S1.784
     [Google Scholar]
  22. ChengY. HeC. WangM. Targeting epigenetic regulators for cancer therapy: Mechanisms and advances in clinical trials.Signal Transduct. Target. Ther.2019416210.1038/s41392‑019‑0095‑031871779
     [Google Scholar]
  23. WangY. YanL. ZhangZ. Epigenetic regulation and its therapeutic potential in pulmonary hypertension.Front. Pharmacol.2018924110.3389/fphar.2018.0024129615911
     [Google Scholar]
  24. RayA. StellohC. LiuY. Histone modifications and their contributions to hypertension.Hypertension202481222923910.1161/HYPERTENSIONAHA.123.2175538031837
     [Google Scholar]
  25. Valdespino-GomezV.M. ValdespinoP.M. Potential of epigenetic therapies in the management of solid tumors.Cancer Manag. Res.2015724125110.2147/CMAR.S7035826346546
     [Google Scholar]
  26. KalebicT. Epigenetic transitions: Towards therapeutic targets.Expert Opin. Ther. Targets20037669369910.1517/14728222.7.6.69314640906
     [Google Scholar]
  27. AhujaN. EaswaranH. BaylinS.B. Harnessing the potential of epigenetic therapy to target solid tumors.J. Clin. Invest.20141241566310.1172/JCI6973624382390
     [Google Scholar]
  28. WangX. TengX. LuoC. KongL. Mechanisms and advances of epigenetic regulation in cardiovascular disease.Front Biosci-Landmark202429620510.31083/j.fbl290620538940023
     [Google Scholar]
  29. FriebeA. SchultzG. KoeslingD. Stimulation of soluble guanylate cyclase by superoxide dismutase is mediated by NO.Biochem. J.1998335352753110.1042/bj33505279794791
     [Google Scholar]
  30. StaschJ.P. PacherP. EvgenovO.V. Soluble guanylate cyclase as an emerging therapeutic target in cardiopulmonary disease.Circulation2011123202263227310.1161/CIRCULATIONAHA.110.98173821606405
     [Google Scholar]
  31. LiX. SongL. LuZ. Integrative analyses of whole-transcriptome sequencing reveals CeRNA regulatory network in pulmonary hypertension treated with FGF21.Int. Immunopharmacol.202413211192510.1016/j.intimp.2024.11192538579562
     [Google Scholar]
  32. PatelD. AlhawajR. KellyM.R. Potential role of mitochondrial superoxide decreasing ferrochelatase and heme in coronary artery soluble guanylate cyclase depletion by angiotensin II.Am. J. Physiol. Heart Circ. Physiol.201631011H1439H144710.1152/ajpheart.00859.201527037373
     [Google Scholar]
  33. ElhemielyA.A. YahiaR. GadA.M. Naringenin alleviates reproductive toxicity evoked by lead acetate via TGFβ/AKT/mTOR pathway.J. Biochem. Mol. Toxicol.202310.1002/jbt.23335
     [Google Scholar]
  34. BorahK. SharmaS. SillaY. Identification of plant-based lead compounds for Alzheimer’s therapy through bioinformatics.Comput. Biol. Chem.20197835936610.1016/j.compbiolchem.2018.12.01230677568
     [Google Scholar]
  35. VetterM. ChenZ.J. ChangG.D. CheD. LiuS. ChangC.H. Cyclosporin A disrupts bradykinin signaling through superoxide.Hypertension20034151136114210.1161/01.HYP.0000068201.48340.3B12695417
     [Google Scholar]
  36. GupteS.A. RupawallaT. Mohazzab-HK.M. WolinM.S. Regulation of NO-elicited pulmonary artery relaxation and guanylate cyclase activation by NADH oxidase and SOD.Am. J. Physiol.19992765H1535H154210330236
     [Google Scholar]
  37. TawaM. GeddawyA. ShimosatoT. IwasakiH. ImamuraT. OkamuraT. Soluble guanylate cyclase redox state under hypoxia or hypoxia/reoxygenation in isolated monkey coronary arteries.J. Pharmacol. Sci.2014125216917510.1254/jphs.14046FP24859780
     [Google Scholar]
  38. SchermulyR.T. StaschJ-P. PullamsettiS.S. Expression and function of soluble guanylate cyclase in pulmonary arterial hypertension.Eur. Respir. J.200832488189110.1183/09031936.0011440718550612
     [Google Scholar]
  39. ZhaoS. GaoY. WangH. A novel glycoprotein from Auricularia polytricha protects against lead-induced hepatotoxicity.Front. Nutr.2023101144346
     [Google Scholar]
  40. NaithaniU. GuleriaV. Integrative computational approaches for lead compound discovery and evaluation.Front Drug Discov2024
     [Google Scholar]
  41. KokovK.V. EgorovaB.V. GermanM.N. 212Pb: Production approaches and targeted therapy applications.Pharmaceutics202214118910.3390/pharmaceutics1401018935057083
     [Google Scholar]
  42. HassanE.H. El-NeweshyM. HassanM. NoreldinA. Thymoquinone mitigates testicular toxicity from lead exposure via antioxidative pathways.Life Sci.201923013214010.1016/j.lfs.2019.05.06731136753
     [Google Scholar]
  43. PrivieroF.B.M. ZemseS.M. TeixeiraC.E. WebbR.C. WebbR. Oxidative stress impairs vasorelaxation induced by the soluble guanylyl cyclase activator BAY 41-2272 in spontaneously hypertensive rats.Am. J. Hypertens.200922549349910.1038/ajh.2009.1819247264
     [Google Scholar]
  44. Nozik-GrayckE. WoodsC. TaylorJ.M. Selective depletion of vascular EC-SOD augments chronic hypoxic pulmonary hypertension.Am. J. Physiol. Lung Cell. Mol. Physiol.201430711L868L87610.1152/ajplung.00096.201425326578
     [Google Scholar]
  45. LoganathanS. Korkmaz-IcözS. RadovitsT. Effects of soluble guanylate cyclase activation on heart transplantation in a rat model.J. Heart Lung Transplant.201534101346135310.1016/j.healun.2015.05.00626210750
     [Google Scholar]
  46. AziziM. AmarL. MénardJ. Aldosterone synthase inhibition in humans.Nephrol. Dial. Transplant.2013281364310.1093/ndt/gfs38823045428
     [Google Scholar]
  47. MulateroP. WurznerG. GroesslM. VogtB. BrunnerH. PS-C37-5: New therapeutic perspectives for blood pressure control: Dexfadrostat phosphate, a novel aldosterone synthase inhibitor, in patients with primary aldosteronism.J. Hypertens.202341Suppl. 1e486e48710.1097/01.hjh.0000917888.30409.8d
     [Google Scholar]
  48. HakkiT. HübelK. WaldmannH. BernhardtR. The development of a whole-cell based medium throughput screening system for the discovery of human aldosterone synthase (CYP11B2) inhibitors: Old drugs disclose new applications for the therapy of congestive heart failure, myocardial fibrosis and hypertension.J. Steroid Biochem. Mol. Biol.20111251-212012810.1016/j.jsbmb.2010.12.01121193036
     [Google Scholar]
  49. OmataK. SatohF. MorimotoR. Cellular and genetic causes of idiopathic hyperaldosteronism.Hypertension201872487488010.1161/HYPERTENSIONAHA.118.1108630354720
     [Google Scholar]
  50. MeredithE.L. KsanderG. MonovichL.G. Discovery and in vivo evaluation of potent dual CYP11B2 (aldosterone synthase) and CYP11B1 inhibitors.ACS Med. Chem. Lett.20134121203120710.1021/ml400324c24900631
     [Google Scholar]
  51. EhmerP.B. BureikM. BernhardtR. MüllerU. HartmannR.W. Development of a test system for inhibitors of human aldosterone synthase (CYP11B2): Screening in fission yeast and evaluation of selectivity in V79 cells.J. Steroid Biochem. Mol. Biol.200281217317910.1016/S0960‑0760(02)00056‑012137808
     [Google Scholar]
  52. BureikM. HübelK. DrăganC.A. Development of test systems for the discovery of selective human aldosterone synthase (CYP11B2) and 11β-hydroxylase (CYP11B1) inhibitors.Mol. Cell. Endocrinol.20042171-224925410.1016/j.mce.2003.10.02715134825
     [Google Scholar]
  53. ShangP. LiuW. LiuT. Acetyl-11-Keto-β-boswellic acid attenuates prooxidant and profibrotic mechanisms involving transforming growth factor-β1, and improves vascular remodeling in spontaneously hypertensive rats.Sci. Rep.2016613980910.1038/srep3980928009003
     [Google Scholar]
  54. PerkettE.A. PeltonR.W. MeyrickB. GoldL.I. MillerD.A. Expression of transforming growth factor-beta mRNAs and proteins in pulmonary vascular remodeling in the sheep air embolization model of pulmonary hypertension.Am. J. Respir. Cell Mol. Biol.1994111162410.1165/ajrcmb.11.1.80183358018335
     [Google Scholar]
  55. BotneyM.D. BahadoriL. GoldL.I. Vascular remodeling in primary pulmonary hypertension. Potential role for transforming growth factor-beta.Am. J. Pathol.199414422862958311113
     [Google Scholar]
  56. SmithJ.D. BryantS.R. CouperL.L. Soluble transforming growth factor-beta type II receptor inhibits negative remodeling, fibroblast transdifferentiation, and intimal lesion formation but not endothelial growth.Circ. Res.199984101212122210.1161/01.RES.84.10.121210347096
     [Google Scholar]
  57. DerhaschnigU. ShehataM. HerknerH. Increased levels of transforming growth factor-β1 in essential hypertension.Am. J. Hypertens.200215320721110.1016/S0895‑7061(01)02327‑511939608
     [Google Scholar]
  58. RuízortegaM. RodríguezvitaJ. SanchezlopezE. CarvajalG. EgidoJ. TGF-β signaling in vascular fibrosis.Cardiovasc. Res.200774219620610.1016/j.cardiores.2007.02.00817376414
     [Google Scholar]
  59. ShangP. LiuT. LiuW. Telmisartan improves vascular remodeling through ameliorating prooxidant and profibrotic mechanisms in hypertension via the involvement of transforming growth factor-β1.Mol. Med. Rep.20171644537454410.3892/mmr.2017.717728791353
     [Google Scholar]
  60. YungL.M. NikolicI. Paskin-FlerlageS.D. PearsallR.S. KumarR. YuP.B. A selective transforming growth factor-β ligand trap attenuates pulmonary hypertension.Am. J. Respir. Crit. Care Med.201619491140115110.1164/rccm.201510‑1955OC27115515
     [Google Scholar]
  61. PorrecaE. Di FebboC. MincioneG. Increased transforming growth factor-beta production and gene expression by peripheral blood monocytes of hypertensive patients.Hypertension199730113413910.1161/01.HYP.30.1.1349231833
     [Google Scholar]
  62. SharminN. NganwuchuC.C. NasimM.T. Targeting the TGF-β signaling pathway for resolution of pulmonary arterial hypertension.Trends Pharmacol. Sci.202142751051310.1016/j.tips.2021.04.00233966900
     [Google Scholar]
  63. FörstermannU SessaWC Nitric oxide synthases: Regulation and function.Eur Heart J2012337829-837, 837a-837d10.1093/eurheartj/ehr30421890489
     [Google Scholar]
  64. SheselyE.G. MaedaN. KimH.S. Elevated blood pressures in mice lacking endothelial nitric oxide synthase.Proc. Natl. Acad. Sci. USA19969323131761318110.1073/pnas.93.23.131768917564
     [Google Scholar]
  65. WoodK.C. Cortese-KrottM.M. KovacicJ.C. Circulating blood endothelial nitric oxide synthase contributes to the regulation of systemic blood pressure and nitrite homeostasis.Arterioscler. Thromb. Vasc. Biol.20133381861187110.1161/ATVBAHA.112.30106823702660
     [Google Scholar]
  66. MurakamiK. TsuchiyaK. NaruseM. Nitric oxide synthase I immunoreactivity in the macula densa of the kidney is angiotensin II dependent.Kidney Int. Suppl.199763S208S2109407461
     [Google Scholar]
  67. AramiK.M. JameieB. MoosaviS.A. Neuronal Nitric Oxide Synthase.IntechOpen201710.5772/67494
     [Google Scholar]
  68. OhashiY. KawashimaS. HirataK. Hypotension and reduced nitric oxide-elicited vasorelaxation in transgenic mice overexpressing endothelial nitric oxide synthase.J. Clin. Invest.1998102122061207110.1172/JCI43949854041
     [Google Scholar]
  69. SaizL.C. GorrichoJ. GarjónJ. CelayaM.C.C. ErvitiJ. LeacheL. Blood pressure targets for the treatment of people with hypertension and cardiovascular disease.Cochrane Database Syst. Rev.202099CD01031532905623
     [Google Scholar]
  70. PaulisL. UngerT. Novel therapeutic targets for hypertension.Nat. Rev. Cardiol.20107843144110.1038/nrcardio.2010.8520567239
     [Google Scholar]
  71. BhattL.K. SelokarI. RautD. HussainT. Novel targets for hypertension drug discovery.Curr. Hypertens. Rep.20212341910.1007/s11906‑021‑01137‑633783647
     [Google Scholar]
  72. GradmanA.H. Strategies for combination therapy in hypertension.Curr. Opin. Nephrol. Hypertens.201221548649110.1097/MNH.0b013e328356c55122871676
     [Google Scholar]
  73. GaoQ. XuL. CaiJ. New drug targets for hypertension: A literature review.Biochim. Biophys. Acta Mol. Basis Dis.20211867316603710.1016/j.bbadis.2020.16603733309796
     [Google Scholar]
  74. McBrienK. RabiD.M. CampbellN. Intensive and standard blood pressure targets in patients with type 2 diabetes mellitus: Systematic review and meta-analysis.Arch. Intern. Med.2012172171296130310.1001/archinternmed.2012.314722868819
     [Google Scholar]
  75. AhluwaliaM. BangaloreS. Management of hypertension in 2017.Curr. Opin. Cardiol.201732441342110.1097/HCO.000000000000040828346238
     [Google Scholar]
  76. QaseemA. WiltT.J. RichR. Pharmacologic treatment of hypertension in adults aged 60 years or older to higher versus lower blood pressure targets: A clinical practice guideline from the American college of physicians and the American academy of family physicians.Ann. Intern. Med.2017166643043710.7326/M16‑178528135725
     [Google Scholar]
  77. LandaM.S. SchumanM.L. AisicovichM. Valproate decreases transgenerationally blood pressure by affecting thyrotropin-releasing hormone promoter DNA methylation and gene expression in spontaneously hypertensive rat.Mol. Cell. Biochem.202448093794910.1007/s11010‑024‑05001‑438630362
     [Google Scholar]
/content/journals/cppm/10.2174/0118756921349049250324173511
Loading
A Pioneer Review on Epigenetic Modifications in Hypertension: Potential Targets for Novel Therapeutics
Curr. Pharm. and. Per. Med. 22, E18756921349049 (2025); https://doi.org/10.2174/0118756921349049250324173511
/content/journals/cppm/10.2174/0118756921349049250324173511
/content/journals/cppm/10.2174/0118756921349049250324173511
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): DNA methylation; epigenetic modifications; histone modifications; Hypertension; microRNAs; therapeutic targets; vascular function

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