Expresión de los componentes del inflamasoma y su relación con los marcadores de riesgo cardiovascular en personas con infección por HIV-1
Resumen
Objetivo. Establecer si existe correlación entre la expresión de los componentes de los inflamasomas y los marcadores de riesgo cardiovascular en individuos con control de la replicación viral y en aquellos con replicación viral activa con terapia antirretroviral o sin ella.
Materiales y métodos. Se estudiaron 13 individuos con control de la replicación viral y 40 con replicación viral activa (19 sin terapia antirretroviral y 31 con terapia). Se evaluaron los marcadores clásicos de riesgo cardiovascular y se cuantificó mediante RT-PCR la expresión de los componentes de los inflamasomas (NLRP1, NLRP3, NLRC4, AIM2, ASC, IL-1β, IL-18 y caspasa-1), TLR2, TLR4, TGF-β e IL-10.
Resultados. Se observó que los pacientes con replicación viral activa y con terapia antirretroviral presentaron un incremento en la expresión de TLR2, TLR4 e IL-18, comparados con los controladores del HIV-1. Además, mostraron grandes valores de triglicéridos y lipoproteína de muy baja densidad (Very Low Density Lipopretein, VLDL), lo que se correlaciona positivamente con la expresión de los componentes de los inflamasomas NLRP1, NLRP3, NLRC4, AIM2, ASC y caspasa-1.
Conclusión. El aumento en la expresión de los componentes de los inflamasomas en los individuos con replicación viral activa y con terapia antirretroviral se correlacionó con las concentraciones de triglicéridos y VLDL, lo que sugiere el papel de la activación inmunitaria y la terapia antirretroviral en el riesgo cardiovascular.
Descargas
Referencias bibliográficas
Walker BD. Elite control of HIV Infection: Implications for vaccines and treatment. Top HIV Med. 2007;15:134-6.
Gonzalo-Gil E, Ikediobi U, Sutton RE. Mechanisms of virologic control and clinical characteristics of HIV+ elite/viremic controllers. Yale J Biol Med. 2017;90:245-59.
Deeks S, Tracy R, Douek D. Systemic effects of inflammation on health during chronic HIV infection. Immunity. 2013;39:633-45. https://doi.org/10.1016/j.immuni.2013.10.001.Systemic
Deeks S. Immune dysfunction, inflammation, and accelerated aging in patients on antiretroviral therapy. Top HIV Med. 2009;14:118-23
Lucas S, Nelson AM. HIV and the spectrum of human disease. J Pathol. 2015;235:229-41. https://doi.org/10.1002/path.4449
Kedzierska K, Crowe SM. Cytokines and HIV-1: Interactions and clinical implications. Antivir Chem Chemother. 2001;12:133-50. https://doi.org/10.1177/095632020101200301
Ahmad R, Sindhu STA, Toma E, Morisset R, Ahmad A. Elevated levels of circulating interleukin-18 in human immunodeficiency virus-infected individuals: Role of peripheral blood mononuclear cells and implications for AIDS pathogenesis. J Virol. 2002;76:12448-56. https://doi.org/10.1128/jvi.76.24.12448-12456.2002
Granowitz E V, Saget BM, Wang MZ, Dinarello CA, Skolnik PR. Interleukin 1 induces HIV-1 expression in chronically infected U1 cells: Blockade by interleukin 1 receptor antagonist and tumor necrosis factor binding protein type 1. Mol Med. 1995;1:667-77. https://doi.org/10.1007/bf03401607
Shapiro L, Puren AJ, Barton HA, Novick D, Peskind RL, Shenkar R, et al. Interleukin 18 stimulates HIV type 1 in monocytic cells. Proc Natl Acad Sci U S A. 1998;95:12550-5. https://doi.org/10.1073/pnas.95.21.12550
Swingler S, Easton A, Morris A. Cytokine augmentation of HIV-1 LTR-driven gene expression in neural cells. AIDS Res Hum Retroviruses. 1992;8:487-93. https://doi.org/10.1089/aid.1992.8.487
Martínez GJ, Celermajer DS, Patel S. The NLRP3 inflammasome and the emerging role of colchicine to inhibit atherosclerosis-associated inflammation. Atherosclerosis. 2018;269:262-71. https://doi.org/10.1016/j.atherosclerosis.2017.12.027
Mullis C, Swartz TH. NLRP3 Inflammasome signaling as a link between HIV-1 infection and atherosclerotic cardiovascular disease. Front Cardiovasc Med. 2020;7:1-11. https://doi.org/10.3389/fcvm.2020.00095
Yazdi AS, Ghoreschi K. The interleukin-1 family. Adv Exp Med Biol. 2016;941:21-9. https://doi.org/10.1007/978-94-024-0921-5
Broz P, Monack DM. Newly described pattern recognition receptors team up against intracellular pathogens. Nat Rev Immunol. 2013;13:551-65. https://doi.org/10.1038/nri3479
Hernández JC, Latz E, Urcuqui-Inchima S. HIV-1 induces the first signal to activate the NLRP3 inflammasome in monocyte-derived macrophages. Intervirology. 2014;57:36-42. https://doi.org/10.1159/000353902
Feria MG, Taborda NA, Hernández JC, Rugeles MT. HIV replication is associated to inflammasomes activation, IL-1β, IL-18 and caspase-1 expression in GALT and peripheral blood. PLoS One. 2018;13:1-14. https://doi.org/10.1371/journal.pone.0192845
Ahmad F, Mishra N, Ahrenstorf G, Franklin BS, Latz E, Schmidt RE, et al. Evidence of inflammasome activation and formation of monocyte-derived ASC specks in HIV-1 positive patients. AIDS. 2018;32:299-307. https://doi.org/10.1097/QAD.0000000000001693
Bociaga-Jasik M, Polus A, Góralska J, Śliwa A, Raź́ny U, Zdzienicka A, et al. Metabolic complications and selected cytokines in HIV-infected individuals. Pol Arch Med Wewn. 2014;124:27-35. https://doi.org/10.20452/pamw.2073
Umeh OC, Currier JS. Lipids, metabolic syndrome, and risk factors for future cardiovascular disease among HIV-infected patients. Curr HIV/AIDS Rep. 2005;2:132-9. https://doi.org/10.1007/s11904-005-0006-6
Tall AR, Yvan-Charvet L. Cholesterol, inflammation and innate immunity. Nat Rev Immunol. 2015;15:104-16. https://doi.org/10.1038/nri3793
Arias-Pérez R, Álvarez N, Sánchez-Gómez C, Flórez-Álvarez L, Marín-Palma D, Taborda NA, et al. Alteración en la expresión de proteínas transportadoras de colesterol y moléculas inmunomoduladoras en pacientes con VIH-1. Kasmera. 2021;49:1-13. https://doi.org/10.5281/zenodo.4780969
Hoseini Z, Sepahvand F, Rashidi B, Sahebkar A, Masoudifar A, Mirzaei H. NLRP3 inflammasome: Its regulation and involvement in atherosclerosis. J Cell Physiol. 2018;233:2116-32. https://doi.org/10.1002/jcp.25930
Tabares-Guevara J, Villa-Pulgarín J, Hernández JC. Atherosclerosis: Immunopathogenesis and strategies for immunotherapy. Immunotherpay. 2021;13:1. https://doi.org/10.2217/imt-2021-0009
Raposeiras-Roubín S, Triant V. Ischemic heart disease in HIV: An in-depth look at cardiovascular risk. Rev Española Cardiol. 2016;69:1204-13. https://doi.org/10.1016/j.rec.2016.10.005
Zicari S, Sessa L, Cotugno N, Ruggiero A, Morrocchi E, Concato C, et al. Immune activation, inflammation, and non-AIDS co-morbidities in HIV-infected patients under long-term ART. Viruses. 2019;11:1-19. https://doi.org/10.3390/v11030200
Marín-Palma D, Castro GA, Cardona-Arias JA, Urcuqui-Inchima S, Hernández JC. Lower high-density lipoproteins levels during human immunodeficiency virus type 1 infection are associated with increased inflammatory markers and disease progression. Front Immunol. 2018;9:1-12. https://doi.org/10.3389/fimmu.2018.01350
Marín-Palma D, Cardona-Arias JA, Hernández JC. Factores inmunológicos relacionados con VIH-1 en pacientes colombianos. Revista Ciencias de la Salud. 2019;17:245-58. https://doi.org/10.12804/revistas.urosario.edu.co/revsalud/a.7927
Schneider E, Whitmore S, Glynn KM, Domínguez K, Mitsch A, McKenna MT. et al. Revised surveillance case definitions for HIV infection among adults, adolescents, and children aged <18 months and for HIV infection and AIDS among children aged 18 months to <13 years —United States. MMWR Recomm Rep. 2008;57:1-12.
Khera AV, Cuchel M, de la Llera-Moya M, Rodrigues A, Burke MF, Jafri K, et al. Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. N Engl J Med. 2011;364:127-35. https://doi.org/10.1056/nejmoa1001689
Thomas MR, Lip GYH. Novel risk markers and risk assessments for cardiovascular disease. Circ Res. 2017;120:133-49. https://doi.org/10.1161/CIRCRESAHA.116.309955
Yvan-Charvet L, Bonacina F, Guinamard RR, Norata GD. Immunometabolic function of cholesterol in cardiovascular disease and beyond. Cardiovasc Res. 2019;115:1393-407. https://doi.org/10.1093/cvr/cvz127
Golia E, Limongelli G, Natale F, Fimiani F, Maddaloni V, Pariggiano I, et al. Inflammation and cardiovascular disease: From pathogenesis to therapeutic target. Curr Atheroscler Rep. 2014;16:1-7. https://doi.org/10.1007/s11883-014-0435-z
Bandera A, Masetti M, Fabbiani M, Biasin M, Muscatello A, Squillace N, et al. The NLRP3 inflammasome is upregulated in HIV-infected antiretroviral therapy-treated individuals with defective immune recovery. Front Immunol. 2018;9:1-8. https://doi.org/10.3389/fimmu.2018.00214
Toksoy A, Sennefelder H, Adam C, Hofmann S, Trautmann A, Goebeler M, et al. Potent NLRP3 inflammasome activation by the HIV reverse transcriptase inhibitor abacavir. J Biol Chem. 2017;292:2805-14. https://doi.org/10.1074/jbc.M116.749473
Luo H, He J, Qin L, Chen Y, Chen L, Li R, et al. Mycoplasma pneumoniae lipids license TLR-4 for activation of NLRP3 inflammasome and autophagy to evoke a proinflammatory response. Clin Exp Immunol. 2020;203:66-79. https://doi.org/10.1111/cei.13510
Taborda NA, Blanquiceth Y, Urcuqui-Inchima S, Latz E, Hernández JC. High-density lipoproteins decrease proinflammatory activity and modulate the innate immune response. J Interf Cytokine Res. 2019;39:760-70. https://doi.org/10.1089/jir.2019.0029
Libby P. Interleukin-1 beta as a target for atherosclerosis therapy: Biological basis of CANTOS and beyond. J Am Coll Cardiol. 2017;70:2278-89. https://doi.org/10.1016/j.jacc.2017.09.028
Rocha DM, Caldas AP, Oliveira LL, Bressan J, Hermsdorff HH. Saturated fatty acids trigger TLR4-mediated inflammatory response. Atherosclerosis. 2016;244:211-5. https://doi.org/10.1016/j.atherosclerosis.2015.11.015
Hocini H, Bonnabau H, Lacabaratz C, Lefebvre C, Tisserand P, Foucat E, et al. HIV controllers have low inflammation associated with a strong HIV-specific immune response in blood. J Virol. 2019;93:1-14. https://doi.org/10.1128/jvi.01690-18
Hileman CO, Funderburg NT. Inflammation, immune activation, and antiretroviral therapy in HIV. Curr HIV/AIDS Rep. 2017;14:93-100. https://doi.org/10.1007/s11904-017-0356-x
Hsue PY, Waters DD. HIV infection and coronary heart disease: Mechanisms and management. Nat Rev Cardiol. 2019;16:745-59. https://doi.org/10.1038/s41569-019-0219-9
Feinstein MJ, Hsue PY, Benjamin LA, Bloomfield GS, Currier JS, Freiberg MS, et al. Characteristics, prevention, and management of cardiovascular disease in people living with HIV: A scientific statement from the American Heart Association. Circulation. 2019;140:e98-124. https://doi.org/10.1161/CIR.0000000000000695
Hsue PY, Waters DD. Time to recognize HIV infection as a major cardiovascular risk factor. Circulation. 2018;138:1113-5. https://doi.org/10.1161/CIRCULATIONAHA.118.036211
Osuji FN, Onyenekwe CC, Ahaneku JE, Ukibe NR. The effects of highly active antiretroviral therapy on the serum levels of pro-inflammatory and anti-inflammatory cytokines in HIV infected subjects. J Biomed Sci. 2018;25:1-8. https://doi.org/10.1186/s12929-018-0490-9
Theron AJ, Anderson R, Rossouw TM, Steel HC. The role of transforming growth factor beta-1 in the progression of HIV/AIDS and development of Non-AIDS-defining fibrotic disorders. Front Immunol. 2017;8:1-15. https://doi.org/10.3389/fimmu.2017.01461
Orsilles MÁ, Pieri E, Cooke P, Caula C. IL-2 and IL-10 serum levels in HIV-1-infected patients with or without active antiretroviral therapy. Apmis. 2006;114:55-60. https://doi.org/10.1111/j.1600-0463.2006.apm_108.x
Girndt M, Köhler H. Interleukin-10 (IL-10): An update on its relevance for cardiovascular risk. Nephrol Dial Transplant. 2003;18:1976-9. https://doi.org/10.1093/ndt/gfg311
Lu S, Zhong J, Huang K, Zhou H. Association of IL-10-1082A/G polymorphism with cardiovascular disease risk: Evidence from a case–control study to an updated metaanalysis. Mol Genet Genomic Med. 2019;7:1-11. https://doi.org/10.1002/mgg3.888
Yilmaz MI, Solak Y, Saglam M, Cayci T, Acikel C, Unal HU, et al. The relationship between IL-10 levels and cardiovascular events in patients with CKD. Clin J Am Soc Nephrol. 2014;9:1207-16. https://doi.org/10.2215/CJN.08660813
Kaplan RC, Landay AL, Hodis HN, Gange SJ, Norris PJ, Young M, et al. Potential cardiovascular disease risk markers among HIV-infected women initiating antiretroviral treatment. J Acquir Immune Defic Syndr. 2012;60:359-68. https://doi.org/10.1097/QAI.0b013e31825b03be
Masenga S, Elijovich F, Koethe J, Hamooya B, Heimburger D, Munsaka S, et al. Hypertension and metabolic syndrome in HIV-infected patients. Curr Hypertens Rep. 2020;22:1-8. https://doi.org/https://doi.org/10.1007/s1190-020-01089-3
Ji S, Xu Y, Han D, Peng X, Lu X, Brockmeyer NH, et al. Changes in lipid indices in HIV+ cases on HAART. Biomed Res Int. 2019;2019:1-8. https://doi.org/10.1155/2019/2870647
Castro G, León K, Marín-Palma D, Oyuela S, Cataño-Bedoya JU, Duque-Botero J, et al. Evaluation of differences in metabolic and immunologic markers and cardiovascular risk in HIV-1 patients. Revista Ciencias de la Salud. 2021;19:1-18. https://doi.org/https://doi.org/10.12804/revistas.urosario.edu.co/revsalud/a
Algunos artículos similares:
- María Clara Echeverry, Nubia Catalina Tovar, Guillermo Mora, Presencia de anticuerpos contra neurorreceptores cardiacos de acetilcolina muscarínicos tipo II en pacientes con enfermedad de Chagas e implantación de marcapasos , Biomédica: Vol. 29 Núm. 3 (2009)
- Mauricio Beltrán, María Cristina Navas, María Patricia Arbeláez, Jorge Donado, Sergio Jaramillo, Fernando De la Hoz, Cecilia Estrada, Lucía del Pilar Cortés, Amalia de Maldonado, Gloria Rey, Seroprevalencia de infección por virus de la hepatitis B y por virus de la inmunodeficiencia humana en una población de pacientes con múltiples transfusiones en cuatro hospitales, Colombia, Sur América , Biomédica: Vol. 29 Núm. 2 (2009)
- María Patricia Arbeláez, Alexánder Arbeláez, Rubén Darío Gómez, Carlos Rojas, Lázaro Vélez, Sonia Luz Arias, Jorge Nagles, Luz Marina Peláez, Gloria Betancourt, Gloria Velásquez, Efectividad de la profilaxis para enfermedad tuberculosa en pacientes infectados por el virus de la inmunodeficiencia humana, Medellín, 2002-2005 , Biomédica: Vol. 27 Núm. 4 (2007)
- María Teresa Rugeles, Paula A. Velilla, Carlos J. Montoya, Mecanismos de resistencia natural al VIH en seres humanos: un resumen de 10 años de investigación en población colombiana , Biomédica: Vol. 31 Núm. 2 (2011)
- Lauro Figueroa-Valverde, Francisco Díaz-Cedillo, María López-Ramos, Elodia García-Cervera, Karen Quijano-Ascencio, Actividad inotrópica inducida por el derivado carbamacepina-alquino en un modelo de corazón aislado y perfundido a flujo constante , Biomédica: Vol. 31 Núm. 2 (2011)
- Jaiberth Cardona-Arias, Luz Peláez-Vanegas, Juan López-Saldarriaga, Marcela Duque-Molina, Oscar Leal-Álvarez, Calidad de vida relacionada con la salud en adultos con VIH/sida, Medellín, Colombia, 2009 , Biomédica: Vol. 31 Núm. 4 (2011)
- Andrés Páez, Constanza Nuñez, Clemencia García, Jorge Boshell, Epidemiología molecular de epizootias de rabia en Colombia, 1994-2002: evidencia de rabia humana y canina asociada a quirópteros. , Biomédica: Vol. 23 Núm. 1 (2003)
- María Belén Jaimes, Diana C. Cáceres, Fernando de la Hoz, Camilo Gutiérrez, Diana Herrera, Jairo Pinilla, Alexandra Porras, Fabio Rodríguez, Martha Velandia, Factores de riesgo para infección respiratoria aguda baja grave en Bogotá, 2001. , Biomédica: Vol. 23 Núm. 3 (2003)
- Sandra Rincón, Adriana Celis, Leticia Sopó, Adriana Motta, María Caridad Cepero de García, Especies de Malassezia aisladas de pacientes con lesiones dermatológicas , Biomédica: Vol. 25 Núm. 2 (2005)
- Adriana M. Celis, María Caridad Cepero de García, Polimorfismos genéticos de aislamientos del género Malassezia obtenidos en Colombia de pacientes con lesión dermatológica y sin ella. , Biomédica: Vol. 25 Núm. 4 (2005)
| Estadísticas de artículo | |
|---|---|
| Vistas de resúmenes | |
| Vistas de PDF | |
| Descargas de PDF | |
| Vistas de HTML | |
| Otras vistas | |
