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Preclinical Characterization of Pharmacologic NAD+Boosting as a Promising Therapeutic Approach inRheumatoid Arthritis
dc.contributor.author | Pérez Sánchez, Carlos | |
dc.contributor.author | Escudero Contreras, Alejandro | |
dc.contributor.author | Cerdó, Tomás | |
dc.contributor.author | Sánchez-Mendoza, Luz Marina | |
dc.contributor.author | Llamas Urbano, Adrián | |
dc.contributor.author | Arias de la Rosa, Iván | |
dc.contributor.author | Pérez Rodríguez, Miguel | |
dc.contributor.author | Muñoz-Barrera, Laura | |
dc.contributor.author | Ábalos-Aguilera, María del Carmen | |
dc.contributor.author | Barbarroja, Nuria | |
dc.contributor.author | Calvo Gutiérrez, Jerusalém | |
dc.contributor.author | Ortega Castro, María Rafaela | |
dc.contributor.author | Ruiz-Vilchez, Desirée | |
dc.contributor.author | Moreno, Juan Antonio | |
dc.contributor.author | Burón, Isabel | |
dc.contributor.author | González Reyes, José Antonio | |
dc.contributor.author | López-Pedrera, Ch. | |
dc.contributor.author | Villalba, José Manuel | |
dc.date.accessioned | 2024-05-21T10:01:29Z | |
dc.date.available | 2024-05-21T10:01:29Z | |
dc.date.issued | 2023 | |
dc.identifier.uri | http://hdl.handle.net/10396/28351 | |
dc.description.abstract | Objective: We analyzed NAD+ metabolism in patients with rheumatoid arthritis (RA), its association with disease activity and clinical outcomes of RA, and the therapeutic potential of pharmacologic NAD+ boosting. Methods: Our study included 253 participants. In the first cohort, comprising 153 RA patients and 56 healthy donors, we assessed NAD+ levels and NAD+-related gene pathways. We analyzed 92 inflammatory molecules by proximity extension assay. In the second cohort, comprising 44 RA patients starting anti–tumor necrosis factor (anti-TNF) drugs, we evaluated changes in NAD+ levels and their association with clinical response after 3 months. Mechanistic studies were performed ex vivo on peripheral blood mononuclear cells (PBMCs) from patients with RA to test the beneficial effects of NAD+ boosters, such as nicotinamide and nicotinamide riboside. Results: Reduced NAD+ levels were found in RA samples, in line with altered activity and expression of genes involved in NAD+ consumption (sirtuins, poly[ADP-ribose] polymerase, CD38), transport (connexin 43), and biosynthesis (NAMPT, NMNATs). Unsupervised clustering analysis identified a group of RA patients with the highest inflammatory profile, the lowest NAD+ levels, and the highest disease activity (as shown by the Disease Activity Score in 28 joints). NAD+ levels were modulated by anti-TNF therapy in parallel with the clinical response. In vitro studies using PBMCs from RA patients showed that nicotinamide riboside and nicotinamide increased NAD+ levels via NAMPT and NMNAT and reduced their prooxidative, proapoptotic, and proinflammatory status. Conclusión: RA patients display altered NAD+ metabolism, directly linked to their inflammatory and disease activity status, which was reverted by anti-TNF therapy. The preclinical beneficial effects of NAD+ boosters, as shown in leukocytes from RA patients, along with their proven clinical safety, might pave the way for the development of clinical trials using these compounds. | es_ES |
dc.format.mimetype | application/pdf | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Wiley | es_ES |
dc.rights | https://creativecommons.org/licenses/by-nc-nd/4.0/ | es_ES |
dc.source | Perez-Sanchez, C., Escudero-Contreras, A., Cerdó, T., Sánchez-Mendoza, L.M., Llamas-Urbano, A., la Rosa, I.A.-d., Pérez-Rodriguez, M., Muñoz-Barrera, L., del Carmen Abalos-Aguilera, M., Barbarroja, N., Calvo, J., Ortega-Castro, R., Ruiz-Vilchez, D., Moreno, J.A., Burón, M.I., González-Reyes, J.A., Collantes-Estevez, E., Lopez-Pedrera, C. and Villalba, J.M. (2023), Preclinical Characterization of Pharmacologic NAD+ Boosting as a Promising Therapeutic Approach in Rheumatoid Arthritis. Arthritis Rheumatol, 75: 1749-1761. | es_ES |
dc.subject | Rheumatoid arthritis | es_ES |
dc.subject | Inflammation | es_ES |
dc.subject | Anti-TNF-a therapy | es_ES |
dc.subject | Inflammatory diseases | es_ES |
dc.title | Preclinical Characterization of Pharmacologic NAD+Boosting as a Promising Therapeutic Approach inRheumatoid Arthritis | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.relation.publisherversion | https://doi.org/10.1002/art.42528 | es_ES |
dc.relation.projectID | Gobierno de España.ISCIII/PI21/00591 | es_ES |
dc.relation.projectID | Gobierno de España.ISCIII/RICOR-RD21/0002/0033 | es_ES |
dc.relation.projectID | Junta de Andalucía.P20_01367 | es_ES |
dc.relation.projectID | Gobierno de España.ISCIII/PI20/00079 | es_ES |
dc.relation.projectID | Gobierno de España.MINECO/RyC-2017-23437 | es_ES |
dc.relation.projectID | Gobierno de España.AEI/RTI2018-100695-B-I00 | es_ES |
dc.relation.projectID | Gobierno de España.AEI/PID2021-126280OB-I00 | es_ES |
dc.relation.projectID | Junta de Andalucía.BIO-276 | es_ES |
dc.relation.projectID | Junta de Andalucía.1263735-R | es_ES |
dc.relation.projectID | Junta de Andalucía.P18-RT-4264 | es_ES |
dc.relation.projectID | Gobierno de España.ISCIII/PI20/00375 | es_ES |
dc.relation.projectID | Junta de Andalucía.PIGE-0052-2020 | es_ES |
dc.relation.projectID | Gobierno de España.MINECO/RYC-2017-22369 | es_ES |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es_ES |