Skip to content
2000
Volume 21, Issue 13
  • ISSN: 1570-1808
  • E-ISSN: 1875-628X

Abstract

Allograft rejection is one of the main problems that must be overcome. Evidence suggests a role of the local renin-angiotensin system (RAS) in the progress of chronic allograft injury. Angiotensin II, generated by the renin-angiotensin system, is well-known as a major regulator molecule to control the blood pressure and fluid system. Evidence suggests that this bioactive molecule and its receptor increase the risk of tissue injuries and organ transplant rejection through different molecular mechanisms such as activation of innate and cellular immunity, upregulation of inflammatory pathways, and accumulation of extracellular matrix by expression pro-fibrotic molecules like transforming growth factor β (TGF-β) to increase the risk of fibrosis. Based on these findings, AT1R antagonists might have therapeutic potential to prevent the risk of tissue injuries and allograft rejection by regulating immune response, inflammation pathway, and fibrogenesis to improve organ functions.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/lddd/10.2174/1570180820666230915103737
2023-09-25
2025-07-27

  • From This Site

    /content/journals/lddd/10.2174/1570180820666230915103737
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. LechlerR.I. SykesM. ThomsonA.W. TurkaL.A. Organ transplantation—how much of the promise has been realized?Nat. Med.200511660561310.1038/nm1251 15937473
     [Google Scholar]
  2. AhmedE.B. AlegreM.L. ChongA.S. Role of bacterial infections in allograft rejection.Expert Rev. Clin. Immunol.20084228129310.1586/1744666X.4.2.281 20477057
     [Google Scholar]
  3. ClaeysE. VermeireK. Immunosuppressive drugs in organ transplantation to prevent allograft rejection: Mode of action and side effects.J Immunol Sci.2019341421
     [Google Scholar]
  4. SpahnJ.H. LiW. KreiselD. Innate immune cells in transplantation.Curr. Opin. Organ Transplant.2014191141910.1097/MOT.0000000000000041 24316757
     [Google Scholar]
  5. TorresI.B. MoresoF. SarróE. MeseguerA. SerónD. The interplay between inflammation and fibrosis in kidney transplantation.Biomed Res. Int.2014201475060210.1155/2014/750602
     [Google Scholar]
  6. VieroR.M. da SilvaM.G. dos SantosD.C. de CarvalhoM.F.C. de AndradeL.G.M. The role of renin–angiotensin system in the chronic allograft nephropathy: an immunohistochemical study.Ren. Fail.201537582783410.3109/0886022X.2015.1024563 25782922
     [Google Scholar]
  7. HallJ.E. GuytonA.C. MizelleH.L. Role of the renin-angiotensin system in control of sodium excretion and arterial pressure.Acta Physiol. Scand. Suppl.19905914862 2220409
     [Google Scholar]
  8. KurdiM. MelloW.C.D. BoozG.W. Working outside the system: An update on the unconventional behavior of the renin–angiotensin system components.Int. J. Biochem. Cell Biol.20053771357136710.1016/j.biocel.2005.01.012 15833268
     [Google Scholar]
  9. KamoT. AkazawaH. KomuroI. Pleiotropic effects of angiotensin II receptor signaling in cardiovascular homeostasis and aging.Int. Heart J.201556324925410.1536/ihj.14‑429 25912907
     [Google Scholar]
  10. ReinsmoenN.L. Role of angiotensin II type 1 receptor-activating antibodies in solid organ transplantation.Hum. Immunol.201374111474147710.1016/j.humimm.2013.06.034 23831255
     [Google Scholar]
  11. DikalovaA. ClempusR. LassègueB. ChengG. McCoyJ. DikalovS. MartinA.S. LyleA. WeberD.S. WeissD. TaylorW.R. SchmidtH.H.H.W. OwensG.K. LambethJ.D. GriendlingK.K. Nox1 overexpression potentiates angiotensin II-induced hypertension and vascular smooth muscle hypertrophy in transgenic mice.Circulation2005112172668267610.1161/CIRCULATIONAHA.105.538934 16230485
     [Google Scholar]
  12. ShabanianS. KhazaieM. FernsG.A. ArjmandM.H. Local renin-angiotensin system molecular mechanisms in intrauterine adhesions formation following gynecological operations, new strategy for novel treatment.J. Obstet. Gynaecol.20224261613161810.1080/01443615.2022.2036972 35260037
     [Google Scholar]
  13. TavakkoliM. AaliS. KhaledifarB. FernsG.A. KhazaeiM. FekriK. ArjmandM.H. The potential association between the risk of post-surgical adhesion and the activated local angiotensin II type 1 receptors: Need for novel treatment strategies.Gastrointest. Tumors20218310711410.1159/000514614 34307308
     [Google Scholar]
  14. GearaA.S. AzziJ. JurewiczM. AbdiR. The renin-angiotensin system: an old, newly discovered player in immunoregulation.Transplant. Rev.200923315115810.1016/j.trre.2009.04.002 19539879
     [Google Scholar]
  15. HeinzeG. MitterbauerC. RegeleH. KramarR. WinkelmayerW.C. CurhanG.C. OberbauerR. Angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor antagonist therapy is associated with prolonged patient and graft survival after renal transplantation.J. Am. Soc. Nephrol.200617388989910.1681/ASN.2005090955 16481415
     [Google Scholar]
  16. LoganathanL. GopinathK. SankaranarayananV.M. KukretiR. RajendranK. LeeJ-K. Computational and pharmacogenomic insights on hypertension treatment: Rational drug design and optimization strategies.Curr. Drug Targets.20202111833
     [Google Scholar]
  17. WeirM.R. BushC. AndersonD.R. ZhangJ. KeefeD. Antihypertensive efficacy, safety, and tolerability of the oral direct renin inhibitor aliskiren in patients with hypertension: A pooled analysis.J. Am. Soc. Hypertens.200714264277
     [Google Scholar]
  18. MalikS. SuchalK. GamadN. DindaA.K. AryaD.S. Telmisartan ameliorates cisplatin-induced nephrotoxicity by inhibiting MAPK mediated inflammation and apoptosis.Eur. J. Pharmacol.20157485460
     [Google Scholar]
  19. JacobsJ.D. WagnerT. GulottaG. LiaoC. LiY.C. Bissonnette, M Impact of angiotensin II signaling blockade on clinical outcomes in patients with inflammatory bowel disease.Dig. Dis. Sci.2019641938194410.1007/s10620‑019‑5474‑4
     [Google Scholar]
  20. PaxtonW.G. RungeM. HoraistC. CohenC. AlexanderR.W. Immunohistochemical localization of rat angiotensin II AT1 receptor.Am. J. Physiol.19932646F989F5
     [Google Scholar]
  21. GuL. ZhuY. LeeM. NguyenA. RyujinN.T. HuangJ. Angiotensin II receptor inhibition ameliorates liver fibrosis and enhances hepatocellular carcinoma infiltration by effector T cells.Proc. Natl. Acad. Sci.202312019e230070612010.1073/pnas.2300706120
     [Google Scholar]
  22. MastoorZ. Diz-ChavesY. González-MatíasL.C. MalloF. Renin–angiotensin system in liver metabolism: Gender differences and role of incretins.Metabolites202212541110.3390/metabo12050411 35629915
     [Google Scholar]
  23. RajapakshaI. Liver fibrosis, liver cancer, and advances in therapeutic approaches.Livers20222437238610.3390/livers2040028
     [Google Scholar]
  24. LeungP. The peptide hormone angiotensin II: Its new functions in tissues and organs.Curr. Protein Pept. Sci.20045426727310.2174/1389203043379693 15320733
     [Google Scholar]
  25. BatallerR. Sancho-bruP. GinèsP. LoraJ.M. Al-garawiA. SoléM. ColmeneroJ. NicolásJ.M. JiménezW. WeichN. Gutiérrez-ramosJ. ArroyoV. RodésJ. Activated human hepatic stellate cells express the renin-angiotensin system and synthesize angiotensin II.Gastroenterology2003125111712510.1016/S0016‑5085(03)00695‑4 12851877
     [Google Scholar]
  26. LubelJ.S. HerathC.B. BurrellL.M. AngusP.W. Liver disease and the renin-angiotensin system: Recent discoveries and clinical implications.J. Gastroenterol. Hepatol.20082391327133810.1111/j.1440‑1746.2008.05461.x 18557800
     [Google Scholar]
  27. LinH. GeurtsF. HasslerL. BatlleD. Mirabito ColafellaK.M. DentonK.M. ZhuoJ.L. LiX.C. RamkumarN. KoizumiM. MatsusakaT. NishiyamaA. HoogduijnM.J. HoornE.J. DanserA.H.J. Kidney angiotensin in cardiovascular disease: Formation and drug targeting.Pharmacol. Rev.202274346250510.1124/pharmrev.120.000236 35710133
     [Google Scholar]
  28. SuzukiY. Ruiz-OrtegaM. Gomez-GuerreroC. TominoY. EgidoJ. Angiotensin II, the immune system and renal diseases: Another road for RAS?Nephrol. Dial. Transplant.20031881423142610.1093/ndt/gfg223 12897073
     [Google Scholar]
  29. SuzukiY. Ruiz-OrtegaM. LorenzoO. RuperezM. EstebanV. EgidoJ. Inflammation and angiotensin II.Int. J. Biochem. Cell Biol.200335688190010.1016/S1357‑2725(02)00271‑6 12676174
     [Google Scholar]
  30. Ruiz-OrtegaM. RuperezM. LorenzoO. EstebanV. BlancoJ. MezzanoS. EgidoJ. Angiotensin II regulates the synthesis of proinflammatory cytokines and chemokines in the kidney.Kidney Int.20026282S12S2210.1046/j.1523‑1755.62.s82.4.x 12410849
     [Google Scholar]
  31. SuzukiY. Gómez-GuerreroC. ShiratoI. López-FrancoO. Hernández-VargasP. SanjuánG. Ruiz-OrtegaM. SugayaT. OkumuraK. TominoY. RaC. EgidoJ. Susceptibility to T cell-mediated injury in immune complex disease is linked to local activation of renin-angiotensin system: The role of NF-AT pathway.J. Immunol.200216984136414610.4049/jimmunol.169.8.4136 12370342
     [Google Scholar]
  32. KarimiF MalekiM NematbakhshM View of the reninangiotensin system in acute kidney injury induced by renal ischemia-reperfusion injury.J Renin Angiotensin Aldosterone Syst.2022202210.1155/2022/9800838
     [Google Scholar]
  33. NahmodK.A. VermeulenM.E. RadienS. SalamoneG. GamberaleR. Fernández-CalottiP. AlvarezA. NahmodV. GiordanoM. GeffnerJ.R. Control of dendritic cell differentiation by angiotensin II.FASEB J.200317311910.1096/fj.02‑0755fje 12514109
     [Google Scholar]
  34. Rodríguez-IturbeB. PonsH. Herrera-AcostaJ. JohnsonR.J. Role of immunocompetent cells in nonimmune renal diseases.Kidney Int.20015951626164010.1046/j.1523‑1755.2001.0590051626.x 11318933
     [Google Scholar]
  35. MezzanoS.A. Ruiz-OrtegaM. EgidoJ. Angiotensin II and renal fibrosis.Hypertension200138363563810.1161/hy09t1.094234 11566946
     [Google Scholar]
  36. NazariS.E. NaimiH. Sayyed-HosseinianS.H. VahediE. DaghianiM. AsgharzadehF. Askarnia-FaalM.M. AvanA. KhazaeiM. HassanianS.M. Effect of angiotensin II pathway inhibitors on post-surgical adhesion band formation: A potential repurposing of old drugs.Injury202253113642364910.1016/j.injury.2022.08.046 36045032
     [Google Scholar]
  37. CapolongoG. CapassoG. ViggianoD. A shared nephroprotective mechanism for renin-angiotensin-system inhibitors, sodium-glucose co-transporter 2 inhibitors, and vasopressin receptor antagonists: Immunology meets hemodynamics.Int. J. Mol. Sci.2022237391510.3390/ijms23073915 35409276
     [Google Scholar]
  38. WeinstockJ.V. KassabJ. Chemotactic response of splenic mononuclear cells to angiotensin II in murine schistosomiasis.J. Immunol.198613762020202410.4049/jimmunol.137.6.2020 3091696
     [Google Scholar]
  39. SuzukiY. Lopez-FrancoO. Gomez-GarreD. TejeraN. Gomez-GuerreroC. SugayaT. BernalR. BlancoJ. OrtegaL. EgidoJ. Renal tubulointerstitial damage caused by persistent proteinuria is attenuated in AT1-deficient mice: Role of endothelin-1.Am. J. Pathol.200115951895190410.1016/S0002‑9440(10)63036‑2 11696450
     [Google Scholar]
  40. JohnsonR.J. Herrera-AcostaJ. SchreinerG.F. Rodríguez-IturbeB. Subtle acquired renal injury as a mechanism of salt-sensitive hypertension.N. Engl. J. Med.20023461291392310.1056/NEJMra011078 11907292
     [Google Scholar]
  41. HisadaY. SugayaT. TanakaS. SuzukiY. RaC. KimuraK. FukamizuA. An essential role of angiotensin II receptor type 1a in recipient kidney, not in transplanted peripheral blood leukocytes, in progressive immune-mediated renal injury.Lab. Invest.20018191243125110.1038/labinvest.3780338 11555672
     [Google Scholar]
  42. EmdinM. FatiniC. MirizziG. PolettiR. BorrelliC. PronteraC. LatiniR. PassinoC. ClericoA. VergaroG. Biomarkers of activation of renin-angiotensin-aldosterone system in heart failure: how useful, how feasible?Clin. Chim. Acta2015443859310.1016/j.cca.2014.10.031 25445411
     [Google Scholar]
  43. OkunukiY. UsuiY. NagaiN. KezukaT. IshidaS. TakeuchiM. GotoH. Suppression of experimental autoimmune uveitis by angiotensin II type 1 receptor blocker telmisartan.Invest. Ophthalmol. Vis. Sci.20095052255226110.1167/iovs.08‑2649 19136706
     [Google Scholar]
  44. CrowleyS.D. VasievichM.P. RuizP. GouldS.K. ParsonsK.K. PazminoA.K. FacemireC. ChenB.J. KimH.S. TranT.T. PisetskyD.S. BarisoniL. Prieto-CarrasqueroM.C. JeanssonM. FosterM.H. CoffmanT.M. Glomerular type 1 angiotensin receptors augment kidney injury and inflammation in murine autoimmune nephritis.J. Clin. Invest.2009119494395310.1172/JCI34862 19287096
     [Google Scholar]
  45. WarnerF.J. LubelJ.S. McCaughanG.W. AngusP.W. Liver fibrosis: A balance of ACEs?Clin. Sci.2007113310911810.1042/CS20070026 17600527
     [Google Scholar]
  46. DechendR. DragunD. HerseF. RiemekastenG. Schulze-ForsterK. MüllerD.N. Activating autoantibodies against the AT1-receptor in vascular disease.Transplantationsmedizin.20122412026
     [Google Scholar]
  47. NeishabouriA. Soltani KhaboushanA. DaghighF. KajbafzadehA.M. Majidi ZolbinM. Decellularization in tissue engineering and regenerative medicine: Evaluation, modification, and application methods.Front. Bioeng. Biotechnol.20221080529910.3389/fbioe.2022.805299 35547166
     [Google Scholar]
  48. YamamotoS. YamamotoS. AkaiT. SasaharaM. KurodaS. Differentiation of fibroblasts into myofibroblasts in the arachnoid membrane of moyamoya disease.Stroke202253113465347310.1161/STROKEAHA.122.039961 36039752
     [Google Scholar]
  49. RiederF. FiocchiC. Intestinal fibrosis in inflammatory bowel disease: Progress in basic and clinical science.Curr. Opin. Gastroenterol.200824446246810.1097/MOG.0b013e3282ff8b36 18622160
     [Google Scholar]
  50. RadwanskaA. CottageC.T. PirasA. Overed-SayerC. SihlbomC. BudidaR. WrenchC. ConnorJ. MonkleyS. HazonP. SchluterH. ThomasM.J. HogaboamC.M. MurrayL.A. Increased expression and accumulation of GDF15 in IPF extracellular matrix contribute to fibrosis.JCI Insight2022716e15305810.1172/jci.insight.153058 35993367
     [Google Scholar]
  51. ZhangY. FengW. PengX. ZhuL. WangZ. ShenH. ChenC. XiaoL. LiS. ZhaoY. LinM. HuangY. LongH. LiangJ. Parthenolide alleviates peritoneal fibrosis by inhibiting inflammation via the NF-κB/TGF-β/Smad signaling axis.Lab. Invest.2022102121346135410.1038/s41374‑022‑00834‑3
     [Google Scholar]
  52. WangR. GuoT. LiJ. Mechanisms of peritoneal mesothelial cells in peritoneal adhesion.Biomolecules20221210149810.3390/biom12101498 36291710
     [Google Scholar]
  53. Zuñiga-AguilarE. Ramírez-FernándezO. Fibrosis and hepatic regeneration mechanism.Transl. Gastroenterol. Hepatol.20227910.21037/tgh.2020.02.21 35243118
     [Google Scholar]
  54. CobbM.S. TaoS. ShorttK. GirgisM. HauptmanJ. SchriewerJ. ChinZ. DorfmanE. CampbellK. HeruthD.P. ShohetR.V. DawnB. KonorevE.A. Smad3 promotes adverse cardiovascular remodeling and dysfunction in doxorubicin-treated hearts.Am. J. Physiol. Heart Circ. Physiol.20223236H1091H110710.1152/ajpheart.00312.2022 36269647
     [Google Scholar]
  55. YoshidaK. MatsuzakiK. MoriS. TahashiY. YamagataH. FurukawaF. SekiT. NishizawaM. FujisawaJ. OkazakiK. Transforming growth factor-β and platelet-derived growth factor signal via c-Jun N-terminal kinase-dependent Smad2/3 phosphorylation in rat hepatic stellate cells after acute liver injury.Am. J. Pathol.200516641029103910.1016/S0002‑9440(10)62324‑3 15793284
     [Google Scholar]
  56. MurphyA.M. WongA.L. BezuhlyM. Modulation of angiotensin II signaling in the prevention of fibrosis.Fibrogenesis Tissue Repair201581710.1186/s13069‑015‑0023‑z 25949522
     [Google Scholar]
  57. NangakuM. FujitaT. Activation of the renin-angiotensin system and chronic hypoxia of the kidney.Hypertens. Res.200831217518410.1291/hypres.31.175 18360035
     [Google Scholar]
  58. HigginsD.F. KimuraK. BernhardtW.M. ShrimankerN. AkaiY. HohensteinB. SaitoY. JohnsonR.S. KretzlerM. CohenC.D. EckardtK.U. IwanoM. HaaseV.H. Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial-to-mesenchymal transition.J. Clin. Invest.2007117123810382010.1172/JCI30487 18037992
     [Google Scholar]
  59. AfrozeS.H. MunshiM.K. MartínezA.K. UddinM. GergelyM. SzynkarskiC. GuerrierM. NizamutdinovD. DostalD. GlaserS. Activation of the renin-angiotensin system stimulates biliary hyperplasia during cholestasis induced by extrahepatic bile duct ligation.Am. J. Physiol. Gastrointest. Liver Physiol.20153088G691G70110.1152/ajpgi.00116.2014 25678505
     [Google Scholar]
  60. CzechowskaG. CelinskiK. KorolczukA. WojcickaG. DudkaJ. BojarskaA. MadroA. BrzozowskiT. The effect of the angiotensin II receptor, type 1 receptor antagonists, losartan and telmisartan, on thioacetamide-induced liver fibrosis in rats.J. Physiol. Pharmacol.2016674575586 27779478
     [Google Scholar]
  61. DragunD. MüllerD.N. BräsenJ.H. FritscheL. Nieminen-KelhäM. DechendR. KintscherU. RudolphB. HoebekeJ. EckertD. MazakI. PlehmR. SchönemannC. UngerT. BuddeK. NeumayerH.H. LuftF.C. WallukatG. Angiotensin II type 1-receptor activating antibodies in renal-allograft rejection.N. Engl. J. Med.2005352655856910.1056/NEJMoa035717 15703421
     [Google Scholar]
  62. BenigniA. MorigiM. RemuzziG. Kidney regeneration.Lancet201037597221310131710.1016/S0140‑6736(10)60237‑1 20382327
     [Google Scholar]
  63. PerryM.E. CheeM.M. FerrellW.R. LockhartJ.C. SturrockR.D. Angiotensin receptor blockers reduce erythrocyte sedimentation rate levels in patients with rheumatoid arthritis.Ann. Rheum. Dis.200867111646164710.1136/ard.2007.082917 18854516
     [Google Scholar]
  64. Shokrian ZeiniM. HaddadiN.S. ShayanM. Shokrian ZeiniM. KazemiK. SolaimanianS. AbdollahifarM.A. HedayatyanfardK. DehpourA.R. Losartan ointment attenuates imiquimod-induced psoriasis-like inflammation.Int. Immunopharmacol.202110010816010.1016/j.intimp.2021.108160 34583123
     [Google Scholar]
  65. MaedaA. OkazakiT. InoueM. KitazonoT. YamasakiM. LemonnierF.A. OzakiS. Immunosuppressive effect of angiotensin receptor blocker on stimulation of mice CTLs by angiotensin II.Int. Immunopharmacol.20099101183118810.1016/j.intimp.2009.06.006 19540938
     [Google Scholar]
  66. PlattenM. YoussefS. HurE.M. HoP.P. HanM.H. LanzT.V. PhillipsL.K. GoldsteinM.J. BhatR. RaineC.S. SobelR.A. SteinmanL. Blocking angiotensin-converting enzyme induces potent regulatory T cells and modulates TH1- and TH17-mediated autoimmunity.Proc. Natl. Acad. Sci.200910635149481495310.1073/pnas.0903958106 19706421
     [Google Scholar]
  67. ArjmandM-H. Zahedi-AvvalF. BarnehF. MousaviS.H. AsgharzadehF. HashemzehiM. Intraperitoneal administration of telmisartan prevents postsurgical adhesion band formation.J. Surg. Res.2020248171181
     [Google Scholar]
  68. GuerraG.C. AraújoA.A. LiraG.A. MeloM.N. SoutoK.K. FernandesD. Telmisartan decreases inflammation by modulating TNF-α, IL-10, and RANK/RANKL in a rat model of ulcerative colitis.Pharmacol. Rep.201567520526
     [Google Scholar]
  69. AnJ. NakajimaT. KubaK. Kimura, AJHR Losartan inhibits LPS-induced inflammatory signaling through a PPARγ-dependent mechanism in human THP-1 macrophages.Hypertens. Res.201033883183510.1038/hr.2010.79
     [Google Scholar]
  70. OpelzG. Treatment of kidney transplant recipients with ACEi/ARB and risk of respiratory tract cancer: A collaborative transplant study report.Am. J. Transplant.2011111124832489
     [Google Scholar]
  71. GoldsteinM.R. MascitelliL. Angiotensin-receptor blockade, cancer, and concerns.Lancet Oncol.2010119817818
     [Google Scholar]
  72. ThillyN. BayatS. AllaF. KesslerM. BriançonS. Determinants and patterns of renin–angiotensin system inhibitors’ prescription in the first year following kidney transplantation.Clin. Transplant.2008224439446
     [Google Scholar]
  73. Renoprotective effect of early inhibition of the renin-angiotensin system in renal transplant recipients. In: Montanaro, D.; Gropuzzo, M.; Tulissi, P.; Vallone, C.; Boscutti, G.; Mioni, R., Eds.; Transplantation Proceedings.Elsevier2005
     [Google Scholar]
/content/journals/lddd/10.2174/1570180820666230915103737
Loading
The Angiotensin Type 1 Receptor: A Drug Target to Reduce the Risk of Organ Transplant Rejection
Letters in Drug Design & Discovery 21, 2537 (2024); https://doi.org/10.2174/1570180820666230915103737
/content/journals/lddd/10.2174/1570180820666230915103737
/content/journals/lddd/10.2174/1570180820666230915103737
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): angiotensin II; angiotensin type 1-receptor; fibrosis; inflammation; Organ transplant rejection; pro-fibrotic molecules

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