Dengue y endotelio: una mirada desde las implicaciones fisiopatológicas de la activación endotelial en el dengue, hasta sus posibilidades terapéuticas
Barra lateral del artículo
Contenido principal del artículo
Resumen
Introducción: El dengue es una enfermedad viral febril muy difundida en el mundo; casi la mitad de la población mundial, alrededor de cuatro billones de personas, vive en áreas con riesgo de dengue; y es a menudo una causa principal de enfermedad en las áreas con riesgo. El dengue es causado por un conjunto de cuatro serotipos de virus con el mismo nombre (Dengue 1, Dengue 2, Dengue 3 y Dengue 4). Este virus es transmitido por la picadura de la hembra infectada de los mosquitos Aedes aegypti y Aedes albopictus. No existe un medicamento específico para tratar el dengue, el manejo de la enfermedad es hasta la fecha sintomático, por lo que es urgente la búsqueda de alternativas terapéuticas específicas para el virus o para los mecanismos fisiopatológicos responsables de las formas graves de esta enfermedad. El objetivo de este estudio fue recopilar las evidencias experimentales significativas de la importancia de la activación endotelial en la fisiopatología del dengue, disponibles en la literatura científica. Materiales y métodos: Se realizó una búsqueda de literatura en inglés en las bases de datos Pubmed, Scopus y ScienceDirect, con las palabras claves: Dengue, endotelio, fisiopatología, activación endotelial. Resultados: Las evidencias experimentales han permitido demostrar que la disfunción endotelial es el núcleo de las manifestaciones clínicas de las formas de dengue grave. Discusión: El establecimiento de mecanismos fisiopatológicos a nivel de la célula endotelial, han permitido evidenciar numerosos blancos terapéuticos para el dengue, que es necesario empezar a validar con estudios clínicos.
Detalles del artículo
Citas
Tsheten T, Clements ACA, Gray DJ, Adhikary RK, Furuya-Kanamori L, Wangdi K. Clinical predictors of severe dengue: a systematic review and meta-analysis. Infect Dis Poverty 2021;10:123).( Gwee XWS, Chua PEY, Pang J. Global dengue importation: a systematic review. BMC Infect Dis. 2021 Oct 19;21(1):1078. PMID: 34666692; PMCID: PMC8524397) https://doi.org/10.1186/s40249-021-00908-2
Halstead S. Recent advances in understanding dengue. F1000Res. 2019 Jul 31;8:F1000 Faculty Rev-1279. PMID: 31448083; PMCID: PMC6676504. https://doi.org/10.12688/f1000research.19197.1
Tsheten T, Clements ACA, Gray DJ, Adhikary RK, Furuya-Kanamori L, Wangdi K. Clinical predictors of severe dengue: a systematic review and meta-analysis. Infect Dis Poverty 2021;10:123. https://doi.org/10.1186/s40249-021-00908-2
Gwee XWS, Chua PEY, Pang J. Global dengue importation: a systematic review. BMC Infect Dis. 2021 Oct 19;21(1):1078. PMID: 34666692; PMCID: PMC8524397. https://doi.org/10.1186/s12879-021-06449-1
Huang CH, Tsai YT, Wang SF, Wang WH, Chen YH. Dengue vaccine: an update. Expert Rev Anti Infect Ther. 2021 Dec;19(12):1495-1502. Epub 2021 Jul 13. PMID: 34182875. https://doi.org/10.1080/14787210.2021.1949983
Shukla R, Ramasamy V, Shanmugam RK, Ahuja R, Khanna N. AntibodyDependent Enhancement: A Challenge for Developing a Safe Dengue Vaccine. Front Cell Infect Microbiol. 2020 Oct 22;10:572681. PMID: 33194810; PMCID: PMC7642463), https://doi.org/10.3389/fcimb.2020.572681
Shukla R, Beesetti H, Brown JA, Ahuja R, Ramasamy V, Shanmugam RK, Poddar A, Batra G, Krammer F, Lim JK, Kale S, Lal AA, Swaminathan S, Khanna N. Dengue and Zika virus infections are enhanced by live attenuated dengue vaccine but not by recombinant DSV4 vaccine candidate in mouse models. EBioMedicine. 2020 Oct;60:102991. Epub 2020 Sep 16. PMID: 32949997; PMCID: PMC7501058. https://doi.org/10.1016/j.ebiom.2020.102991
Lama S., Burkeb D., Capedingc M., Chongd C., Coudevillee L., Farrarf J., et al. Preparing for introduction of a dengue vaccine: Recommendations from the 1 st Dengue v2V Asia-Pacific Meeting. Vaccine. 2011; 29: 9417-9422. https://doi.org/10.1016/j.vaccine.2011.08.047
Escudero-Flórez, M.; Torres-Hoyos, D.; Miranda-Brand, Y.; GallegoGómez, J.C.; Vicente-Manzanares, M. Dengue Virus Infection Alters Inter-Endothelial Junctions and Promotes Endothelial-Mesenchymal- Transition-Like Changes in Human Microvascular Endothelial Cells. Viruses 2023, 15, 1437. https://doi.org/10.3390/v15071437
Luplertlop N, Missé D, Bray D, Deleuze V, Gonzalez JP, Leardkamolkarn V, Yssel H, Veas F. Dengue-virus-infected dendritic cells trigger vascular leakage through metalloproteinase overproduction. EMBO Rep. 2006 Nov;7(11):1176-81. Epub 2006 Oct 6. Erratum in: EMBO Rep. 2006 Dec;7(12):1290. Luplerdlop, Natthanej [corrected to Luplertlop, Natthanej]. PMID: 17028575; PMCID: PMC1679776). https://doi.org/10.1038/sj.embor.7400814
Álvarez M., González A., Díaz D., Morier L., Guzmán M. Normalización de la técnica de neutralización por placas en las células Vero para los virus del dengue. REV CUBANA MED TROPICAL. 2010; 62(2):138-145.
Kukreti H., Chaudhary A., Rautela R., Anand R., Mittal V., Chhabra M., et al. Emergence of an independent lineage of dengue virus type 1 (DENV-1) and its co-circulation with predominant DENV-3 during the 2006 dengue fever outbreak in Delhi. International Journal of Infectious Diseases 2008 12: 542-549. https://doi.org/10.1016/j.ijid.2008.02.009
Deas T., Binduga I.,Tilgner M., Ren P., Stein D., Moulton H., et al. Inhibition of Flavivirus Infections by Antisense Oligomers Specifically Suppressing Viral Translation and RNA Replication. Journal of Virology. 2005; 79 (8): 4599-4609. https://doi.org/10.1128/JVI.79.8.4599-4609.2005
Nanaware N, Banerjee A, Mullick Bagchi S, Bagchi P, Mukherjee A. Dengue Virus Infection: A Tale of Viral Exploitations and Host Responses. Viruses. 2021 Sep 30;13(10):1967. PMID: 34696397; PMCID: PMC8541669. https://doi.org/10.3390/v13101967
Subramaniam S, Scharrer I. Procoagulant activity during viral infections. Front Biosci (Landmark Ed). 2018 Jan 1;23(6):1060-1081. PMID: 28930589. https://doi.org/10.2741/4633
Glassman PM, Myerson JW, Ferguson LT, Kiseleva RY, Shuvaev VV, Brenner JS, Muzykantov VR. Targeting drug delivery in the vascular system: Focus on endothelium. Adv Drug Deliv Rev. 2020;157:96-117. Epub 2020 Jun 21. PMID: 32579890; PMCID: PMC7306214. https://doi.org/10.1016/j.addr.2020.06.013
Kruger-Genge A, Blocki A, Franke RP, Jung F. Vascular Endothelial Cell Biology: An Update. Int J Mol Sci. 2019 Sep 7;20(18):4411. PMID: 31500313; PMCID: PMC6769656, https://doi.org/10.3390/ijms20184411
Carvajal Carvajal C. El endotelio: estructura, función y disfunción endotelial. Med. leg. Costa Rica [Internet]. 2017 Dec [cited 2023 Sep 12] ; 34( 2 ): 90-100. Available from: http://www.scielo.sa.cr/scielo.php?script=sci_arttext&pid=S1409-00152017000200090&lng=enb
Glassman PM, Myerson JW, Ferguson LT, Kiseleva RY, Shuvaev VV, Brenner JS, Muzykantov VR. Targeting drug delivery in the vascular system: Focus on endothelium. Adv Drug Deliv Rev. 2020;157:96-117. Epub 2020 Jun 21. PMID: 32579890; PMCID: PMC7306214. https://doi.org/10.1016/j.addr.2020.06.013
Jun Zhang. Biomarkers of endothelial activation and dysfunction in cardiovascular diseases. Rev. Cardiovasc. Med. 2022, 23(2), 73. https://doi.org/10.31083/j.rcm2302073
Symons JD, Abel ED. Lipotoxicity contributes to endothelial dysfunction: a focus on the contribution from ceramide. Rev Endocr Metab Disord. 2013 Mar;14(1):59-68. PMID: 23292334; PMCID: PMC4180664. https://doi.org/10.1007/s11154-012-9235-3
Jun Zhang. Biomarkers of endothelial activation and dysfunction in cardiovascular diseases. Rev. Cardiovasc. Med. 2022, 23(2), 73. https://doi.org/10.31083/j.rcm2302073
Steven Daniel Funk, Arif Yurdagul, A. Wayne Orr, "Hyperglycemia and Endothelial Dysfunction in Atherosclerosis: Lessons from Type 1 Diabetes", International Journal of Vascular Medicine, vol. 2012, Article ID 569654, 19 pages, 2012. https://doi.org/10.1155/2012/569654
Fosse JH, Haraldsen G, Falk K, Edelmann R. Endothelial Cells in Emerging Viral Infections. Front Cardiovasc Med. 2021 Feb 24;8:619690. PMID: 33718448; PMCID: PMC7943456. https://doi.org/10.3389/fcvm.2021.619690
Mutiara, Koh SCL, Bachtiar A, Hariman H. The Vascular Endothelium in Patients with Dengue Haemorrhagic Fever. Open Access Maced J Med Sci. 2019 Jul 12;7(14):2221-2225. PMID: 31592071; PMCID: PMC6765093 https://doi.org/10.3889/oamjms.2019.621
Guzman M., Kouri G. Dengue diagnosis, advances and challenges. International Journal of Infectious Diseases. 2004; 8: 69-80. https://doi.org/10.1016/j.ijid.2003.03.003
Young E, Yount B, Pantoja P, Henein S, Meganck RM, McBride J, Munt JE, Baric TJ, Zhu D, Scobey T, Dong S, Tse LV, Martinez MI, Burgos AG, Graham RL, White L, DeSilva A, Sariol CA, Baric RS. A live dengue virus vaccine carrying a chimeric envelope glycoprotein elicits dual DENV2-DENV4 serotype-specific immunity. Nat Commun. 2023 Mar 13;14(1):1371. PMID: 36914616; PMCID: PMC10009830. https://doi.org/10.1038/s41467-023-36702-x
Liu, P., Woda, M., Ennis, F. A., & Libraty, D. H. (2009). Dengue Virus Infection Differentially Regulates Endothelial Barrier Function over Time through Type I Interferon Effects. The Journal of Infectious Diseases, 200(2), 191-201. http://www.jstor.org/stable/40254983. https://doi.org/10.1086/599795
Bhatt P, Sabeena SP, Varma M, Arunkumar G. Current Understanding of the Pathogenesis of Dengue Virus Infection. Curr Microbiol. 2021 Jan;78(1):17-32. Epub 2020 Nov 24. PMID: 33231723; PMCID: PMC7815537. https://doi.org/10.1007/s00284-020-02284-w
Leong AS, Wong KT, Leong TY, Tan PH, Wannakrairot P. The pathology of dengue hemorrhagic fever. Semin Diagn Pathol. 2007 Nov;24(4):227-36. PMID: 18085063. https://doi.org/10.1053/j.semdp.2007.07.002
Basu A, Chaturvedi UC. Vascular endothelium: the battlefield of dengue viruses. FEMS Immunol Med Microbiol. 2008 Aug;53(3):287-99. Epub 2008 Jul 3. PMID: 18522648; PMCID: PMC7110366. https://doi.org/10.1111/j.1574-695X.2008.00420.x
Simmons CP, Farrar JJ, Nguyen vV, Wills B. Dengue. N Engl J Med. 2012 Apr 12;366(15):1423-32. PMID: 22494122. https://doi.org/10.1056/NEJMra1110265
Malavige GN, Ogg GS. Pathogenesis of vascular leak in dengue virus infection. Immunology. 2017 Jul;151(3):261-269. Epub 2017 May 24. PMID: 28437586; PMCID: PMC5461104). https://doi.org/10.1111/imm.12748
Luplertlop N, Missé D, Bray D, Deleuze V, Gonzalez JP, Leardkamolkarn V, Yssel H, Veas F. Dengue-virus-infected dendritic cells trigger vascular leakage through metalloproteinase overproduction. EMBO Rep. 2006 Nov;7(11):1176-81. Epub 2006 Oct 6. Erratum in: EMBO Rep. 2006 Dec;7(12):1290. Luplerdlop, Natthanej [corrected to Luplertlop, Natthanej]. PMID: 17028575; PMCID: PMC1679776. https://doi.org/10.1038/sj.embor.7400814
Srikiatkhachorn A, Kelley JF. Endothelial cells in dengue hemorrhagic fever. Antiviral Res. 2014 Sep;109:160-70. Epub 2014 Jul 12. Erratum in: Antiviral Res. 2015 Feb;114:47. PMID: 25025934; PMCID: PMC4148486. https://doi.org/10.1016/j.antiviral.2014.12.001
Puerta-Guardo H, Glasner DR, Espinosa DA, Biering SB, Patana M, Ratnasiri K, Wang C, Beatty PR, Harris E. Flavivirus NS1 Triggers Tissue-Specific Vascular Endothelial Dysfunction Reflecting Disease Tropism. Cell Rep. 2019 Feb 5;26(6):1598-1613.e8. PMID: 30726741; PMCID: PMC6934102. https://doi.org/10.1016/j.celrep.2019.01.036
Puerta-Guardo H, Glasner DR, Harris E. Dengue Virus NS1 Disrupts the Endothelial Glycocalyx, Leading to Hyperpermeability. PLoS Pathog. 2016 Jul 14;12(7):e1005738. PMID: 27416066; PMCID: PMC4944995. https://doi.org/10.1371/journal.ppat.1005738
Glasner DR, Ratnasiri K, Puerta-Guardo H, Espinosa DA, Beatty PR, Harris E. Dengue virus NS1 cytokine-independent vascular leak is dependent on endothelial glycocalyx components. PLoS Pathog. 2017 Nov 9;13(11):e1006673. PMID: 29121099; PMCID: PMC5679539. https://doi.org/10.1371/journal.ppat.1006673
Barbachano-Guerrero A, Endy TP, King CA. Dengue virus non-structural protein 1 activates the p38 MAPK pathway to decrease barrier integrity in primary human endothelial cells. J Gen Virol. 2020 May;101(5):484-496. Epub 2020 Mar 4. PMID: 32141809. https://doi.org/10.1099/jgv.0.001401
Pan P, Li G, Shen M, Yu Z, Ge W, Lao Z, Fan Y, Chen K, Ding Z, Wang W, Wan P, Shereen MA, Luo Z, Chen X, Zhang Q, Lin L, Wu J. DENV NS1 and MMP-9 cooperate to induce vascular leakage by altering endothelial cell adhesion and tight junction. PLoS Pathog. 2021 Jul 26;17(7):e1008603. PMID: 34310658; PMCID: PMC8341711 https://doi.org/10.1371/journal.ppat.1008603
Lien TS, Sun DS, Wu CY, Chang HH. Exposure to Dengue Envelope Protein Domain III Induces Nlrp3 Inflammasome-Dependent Endothelial Dysfunction and Hemorrhage in Mice. Front Immunol. 2021 Feb 25;12:617251. PMID: 33717109; PMCID: PMC7947687. https://doi.org/10.3389/fimmu.2021.617251
Cipitelli MDC, Paiva IA, Badolato-Correa J, Marinho CF, Fiestas Solorzano VE, da Costa Faria NR, de Azeredo EL, de Souza LJ, da Cunha RV, deOliveira-Pinto LM. Subsets of Cytokines and Chemokines from DENV4-Infected Patients Could Regulate the Endothelial Integrity of Cultured Microvascular Endothelial Cells. Pathogens. 2022 Apr 26;11(5):509. PMID: 35631030; PMCID: PMC9144803. https://doi.org/10.3390/pathogens11050509
Calderón-Peláez MA, Coronel-Ruiz C, Castellanos JE, Velandia-Romero ML. Endothelial Dysfunction, HMGB1, and Dengue: An Enigma to Solve. Viruses. 2022 Aug 12;14(8):1765. PMID: 36016387; PMCID: PMC9414358. https://doi.org/10.3390/v14081765
Oliveira ERA, Povoa TF, Nuovo GJ, Allonso D, Salomao NG, Basilio-deOliveira CA, Geraldo LHM, Fonseca CG, Lima FRS, Mohana-Borges R, Paes MV. Dengue fatal cases present virus-specific response in peripheral organs. Sci Rep. 2017 Nov 22;7(1):16011. PMC5700165. https://doi.org/10.1038/s41598-017-16197-5
Zainal N, Chang CP, Cheng YL, Wu YW, Anderson R, Wan SW, Chen CL, Ho TS, AbuBakar S, Lin YS. Resveratrol treatment reveals a novel role for HMGB1 in regulation of the type 1 interferon response in dengue virus infection. PMCID: PMC5316936.
Chaudhary N, Srivastava S, Dave U, Ojha A, Guchhait P, Chandele A, Patel AK. High-mobility group box 1 protein promotes dengue virus replication by interacting with untranslated regions of viral genome. Virus Res. 2022 Feb;309:198668. Epub 2021 Dec 29. PMID: 34971702. https://doi.org/10.1016/j.virusres.2021.198668
Chaudhary N, Srivastava S, Gupta S, Menon MB, Patel AK. Dengue virus induced autophagy is mediated by HMGB1 and promotes viral propagation. Int J Biol Macromol. 2023 Feb 28;229:624-635. Epub 2022 Dec 29. PMID: 36587643. https://doi.org/10.1016/j.ijbiomac.2022.12.299
Kamau E, Takhampunya R, Li T, Kelly E, Peachman KK, Lynch JA, Sun P, Palmer DR. Dengue virus infection promotes translocation of high mobility group box 1 protein from the nucleus to the cytosol in dendritic cells, upregulates cytokine production and modulates virus replication. J Gen Virol. 2009 Aug;90(Pt 8):1827-1835. Epub 2009 Apr 15. PMID: 19369409. https://doi.org/10.1099/vir.0.009027-0
Medina-Leyte DJ, Zepeda-García O, Domínguez-Pérez M, González-Garrido A, Villarreal-Molina T, Jacobo-Albavera L. Endothelial Dysfunction, Inflammation and Coronary Artery Disease: Potential Biomarkers and Promising Therapeutical Approaches. Int J Mol Sci. 2021 Apr 8;22(8):3850. PMID: 33917744; PMCID: PMC8068178 https://doi.org/10.3390/ijms22083850
Prasad M, Leon M, Lerman LO, Lerman A. Viral Endothelial Dysfunction: A Unifying Mechanism for COVID-19. Mayo Clin Proc. 2021 Dec;96(12):30993108. Epub 2021 Aug 19. PMID: 34863398; PMCID: PMC8373818) https://doi.org/10.1016/j.mayocp.2021.06.027
Fosse JH, Haraldsen G, Falk K, Edelmann R. Endothelial Cells in Emerging Viral Infections. Front Cardiovasc Med. 2021 Feb 24;8:619690. PMID: 33718448; PMCID: PMC7943456 https://doi.org/10.3389/fcvm.2021.619690
Balakrishna Pillai A, JeanPierre AR, Mariappan V, Ranganadin P, S R R. Neutralizing the free radicals could alleviate the disease severity following an infection by positive strand RNA viruses. Cell Stress Chaperones. 2022 May;27(3):189-195. Epub 2022 Apr 3. PMID: 35366756; PMCID: PMC8976658. https://doi.org/10.1007/s12192-022-01269-x
Tang F, Liu D, Zhang L, Xu LY, Zhang JN, Zhao XL, Ao H, Peng C. Targeting endothelial cells with golden spice curcumin: A promising therapy for cardiometabolic multimorbidity. Pharmacol Res. 2023 Nov;197:106953. Epub 2023 Oct 5. PMID: 37804925 https://doi.org/10.1016/j.phrs.2023.106953
Lipskaia L, Hadri L, Lopez JJ, Hajjar RJ, Bobe R. Benefit of SERCA2a gene transfer to vascular endothelial and smooth muscle cells: a new aspect in therapy of cardiovascular diseases. Curr Vasc Pharmacol. 2013 Jul;11(4):465-79. PMID: 23905641; PMCID: PMC6019278 https://doi.org/10.2174/1570161111311040010
Xu SW, Ilyas I, Weng JP. Endothelial dysfunction in COVID-19: an overview of evidence, biomarkers, mechanisms and potential therapies. Acta Pharmacol Sin. 2023 Apr;44(4):695-709. Epub 2022 Oct 17. PMID: 36253560; PMCID: PMC9574180 https://doi.org/10.1038/s41401-022-00998-0
Biering SB, Akey DL, Wong MP, Brown WC, Lo NTN, Puerta-Guardo H, Tramontini Gomes de Sousa F, Wang C, Konwerski JR, Espinosa DA, Bockhaus NJ, Glasner DR, Li J, Blanc SF, Juan EY, Elledge SJ, Mina MJ, Beatty PR, Smith JL, Harris E. Structural basis for antibody inhibition of flavivirus NS1-triggered endothelial dysfunction. Science. 2021 Jan 8;371(6525):194-200. PMID: 33414220; PMCID: PMC8000976. https://doi.org/10.1126/science.abc0476
Aloia AL, Abraham AM, Bonder CS, Pitson SM, Carr JM. Dengue Virus-Induced Inflammation of the Endothelium and the Potential Roles of Sphingosine Kinase-1 and MicroRNAs. Mediators Inflamm. 2015;2015:509306. Epub 2015 Nov 2. PMID: 26609198; PMCID: PMC4644833. https://doi.org/10.1155/2015/509306