Plasma Expression of Carotid Plaque Presence-Related MicroRNAs Is Associated with Inflammation in Patients with Rheumatoid Arthritis

Author:

Llop Dídac123,Paredes Silvia124,Ibarretxe Daiana1235,Taverner Delia4,Plana Núria1235,Rosales Roser13,Masana Lluís1235ORCID,Vallvé Joan Carles123ORCID

Affiliation:

1. Unitat de Recerca de Lípids i Arteriosclerosi, Universitat Rovira i Virgili, 43201 Reus, Catalonia, Spain

2. Institut d’Investigació Sanitària Pere Virgili (IISPV), 43007 Reus, Catalonia, Spain

3. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, 28029 Madrid, Spain

4. Sección de Reumatología, Hospital Universitario Sant Joan, 43204 Reus, Catalonia, Spain

5. Servicio de Medicina Interna, Hospital Universitario Sant Joan, 43204 Reus, Catalonia, Spain

Abstract

Rheumatoid arthritis (RA) is associated with problems beyond the joints such as cardiovascular (CV) disease. MicroRNA-24, -146 and -Let7a are associated with carotid plaque presence in RA patients. We evaluated whether these microRNAs were involved in the inflammatory state of RA, and we studied their gene targets to understand their role in inflammation and atherosclerosis. A total of 199 patients with RA were included. Inflammatory variables such as disease activity score 28 (DAS28) and erythrocyte sedimentation rate (ESR) were quantified. MicroRNAs were extracted from plasma and quantified with qPCR. Multivariate models and classification methods were used for analysis. The multivariate models showed that diminished expression of microRNA-146 was associated with inferior levels of DAS28-ESR, and the decreased expression of microRNA-24, -146 and -Let7a were associated with lowered ESR in the overall cohort. When microRNAs were evaluated globally, a global increase was associated with increased DAS28-ESR and ESR in the overall cohort. Sex-stratified analyses showed different associations of these microRNAs with the inflammatory variables. Finally, random forest models showed that microRNAs have a pivotal role in classifying patients with high and low inflammation. Plasmatic expressions of microRNA-24, -146 and -Let7a were associated with inflammatory markers of RA. These microRNAs are associated with both inflammation and atherosclerosis and are potential therapeutic targets for RA.

Funder

Instituto de Salud Carlos III

European Union

Sociedad Española de Reumatología

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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