Expresión de los componentes del inflamasoma y su relación con los marcadores de riesgo cardiovascular en personas con infección por HIV-1

Kevin León , Damariz Marín-Palma, Salomón Gallego , Crisitina Yepes, Jhonatan Vélez, Gustavo A. Castro, Fabián Jaimes, Natalia Taborda, María Teresa Rugeles, Juan C. Hernández , .

Palabras clave: HIV-1, inflamasomas, cardiopatías, replicación viral

Resumen

Introducción. La infección por el HIV-1 induce un estado de inflamación crónico en el que participan los inflamasomas. El incremento de los parámetros inflamatorios es mayor en individuos con replicación viral activa que en aquellos con control de la replicación viral. Este proceso desencadena alteraciones metabólicas relacionadas con cambios en el perfil lipídico, lo cual podría incrementar el riesgo de eventos cardiovasculares, incluso en pacientes con terapia antirretroviral.
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.

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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

Cómo citar
1.
León K, Marín-Palma D, Gallego S, Yepes C, Vélez J, Castro GA, Jaimes F, Taborda N, Rugeles MT, Hernández JC. Expresión de los componentes del inflamasoma y su relación con los marcadores de riesgo cardiovascular en personas con infección por HIV-1. biomedica [Internet]. 1 de junio de 2022 [citado 26 de junio de 2022];42(2):239-41. Disponible en: https://revistabiomedica.org/index.php/biomedica/article/view/6320

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2022-06-01
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