Personalized cardiovascular risk assessment in Rheumatoid Arthritis patients using circulating molecular profiles and their modulation by TNFi, IL6Ri, and JAKinibs.

Autor:	Muñoz-Barrera L; Rheumatology service/Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/ Reina Sofia University Hospital/ University of Cordoba, Spain., Perez-Sanchez C; Rheumatology service/Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/ Reina Sofia University Hospital/ University of Cordoba, Spain., Ortega-Castro R; Rheumatology service/Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/ Reina Sofia University Hospital/ University of Cordoba, Spain., Corrales S; Rheumatology service/Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/ Reina Sofia University Hospital/ University of Cordoba, Spain., Luque-Tevar M; Rheumatology service/Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/ Reina Sofia University Hospital/ University of Cordoba, Spain., Cerdó T; Rheumatology service/Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/ Reina Sofia University Hospital/ University of Cordoba, Spain., Sanchez-Pareja I; Rheumatology service/Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/ Reina Sofia University Hospital/ University of Cordoba, Spain., Font P; Rheumatology service/Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/ Reina Sofia University Hospital/ University of Cordoba, Spain., Lopez-Mejías R; Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, IDIVAL, Santander, Spain., Calvo J; Rheumatology service/Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/ Reina Sofia University Hospital/ University of Cordoba, Spain., Abalos-Aguilera MC; Rheumatology service/Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/ Reina Sofia University Hospital/ University of Cordoba, Spain., Ruiz-Vilchez D; Rheumatology service/Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/ Reina Sofia University Hospital/ University of Cordoba, Spain., Segui P; Radiology Service, Reina Sofia Hospital/Maimonides Institute for Research in Biomedicine of Cordoba/University of Cordoba, Spain., Merlo C; Rheumatology service/Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/ Reina Sofia University Hospital/ University of Cordoba, Spain., Perez-Venegas J; Virgen Macarena University Hospital, Sevilla, Spain., Ruiz Montesino MD; Virgen Macarena University Hospital, Sevilla, Spain., Rodriguez-Escalera C; Virgen de la Victoria Hospital, Malaga, Spain., Barco CR; Virgen de la Victoria Hospital, Malaga, Spain., Fernandez-Nebro A; Hospital Regional Universitario de Malaga, Malaga, Spain., Vazque NM; Hospital Regional Universitario de Malaga, Malaga, Spain., Marenco JL; Virgen de Valme University Hospital, Sevilla, Spain., Montañes JU; Virgen de Valme University Hospital, Sevilla, Spain., Godoy-Navarrete J; Jaen University Hospital, Spain., Cabezas-Lucena AM; Jaen University Hospital, Spain., Estevez EC; Rheumatology service/Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/ Reina Sofia University Hospital/ University of Cordoba, Spain., Aguirre MA; Rheumatology service/Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/ Reina Sofia University Hospital/ University of Cordoba, Spain., González-Gay MA; Fundacion Jimenez Diaz, Madrid, Spain; Universidad de Cantabria, Santander, Spain., Barbarroja N; Rheumatology service/Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/ Reina Sofia University Hospital/ University of Cordoba, Spain., Escudero-Contreras A; Rheumatology service/Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/ Reina Sofia University Hospital/ University of Cordoba, Spain., Lopez-Pedrera C; Rheumatology service/Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/ Reina Sofia University Hospital/ University of Cordoba, Spain. Electronic address: rosario.lopez.exts@juntadeandalucia.es.
Jazyk:	angličtina
Zdroj:	Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2024 Apr; Vol. 173, pp. 116357. Date of Electronic Publication: 2024 Mar 12.
DOI:	10.1016/j.biopha.2024.116357
Abstrakt:	Background & Objectives: This study aimed to: 1) analyze the inflammatory profile of Rheumatoid Arthritis (RA) patients, identifying clinical phenotypes associated with cardiovascular (CV) risk; 2) evaluate biologic and targeted-synthetic disease-modifying antirheumatic drugs (b-DMARDs and ts-DMARDs': TNFi, IL6Ri, JAKinibs) effects; and 3) characterize molecular mechanisms in immune-cell activation and endothelial dysfunction. Patients & Methods: A total of 387 RA patients and 45 healthy donors were recruited, forming three cohorts: i) 208 RA patients with established disease but without previous CV events; ii) RA-CVD: 96 RA patients with CV events, and iii) 83 RA patients treated with b-DMARDs/ts-DMARDs for 6 months. Serum inflammatory profiles (cytokines/chemokines/growth factors) and NETosis/oxidative stress-linked biomolecules were evaluated. Mechanistic in vitro studies were performed on monocytes, neutrophils and endothelial cells (EC). Results: In the first RA-cohort, unsupervised clustering unveiled three distinct groups: cluster 3 (C3) displayed the highest inflammatory profile, significant CV-risk score, and greater atheroma plaques prevalence. In contrast, cluster 1 (C1) exhibited the lowest inflammatory profile and CV risk score, while cluster 2 (C2) displayed an intermediate phenotype. Notably, 2nd cohort RA-CVD patients mirrored C3's inflammation. Treatment with b-DMARDs or ts-DMARDs effectively reduced disease-activity scores (DAS28) and restored normal biomolecules levels, controlling CV risk. In vitro, serum from C3-RA or RA-CVD patients increased neutrophils activity and CV-related protein levels in cultured monocytes and EC, which were partially prevented by pre-incubation with TNFi, IL6Ri, and JAKinibs. Conclusions: Overall, analyzing circulating molecular profiles in RA patients holds potential for personalized clinical management, addressing CV risk and assisting healthcare professionals in tailoring treatment, ultimately improving outcomes. Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze:	MEDLINE
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