Plasma expression of a microRNA panel is differentially associated with 1H-NMR lipoprotein profile in rheumatoid arthritis patients

Introduction

Rheumatoid arthritis (RA) is an autoimmune and inflammatory disorder that leads to cartilage and bone deterioration. This inflammatory activity causes extra-articular manifestations, including the acceleration of the atherosclerotic process. However, the exact causes of this accelerated process are under investigation. In this study, we compared the advanced lipid profile between patients with RA, patients with metabolic disorders, and controls. We also explored how microRNAs previously associated with subclinical atherosclerosis in RA are linked to these lipid subfractions in RA.

Methods

The study included 219 patients with RA, 82 with metabolic disorders and 64 controls. Clinical evaluations were performed, and blood samples were collected. Quantification of microRNAs (Let7a, 24, 96, 103, 125a, 125b, 132, 146, 191, 223, 425, 451) and measurement of the advanced lipid profile using nuclear magnetic resonance (NMR) were carried out. Kruskal–Wallis tests and multivariate linear models were applied.

Results

Patients with RA exhibited elevated total, large, medium, and small VLDL particles compared to controls. Their LDL subfractions were decreased compared to patients with metabolic disorders, with differences with controls. Patients with RA had fewer and smaller HDL particles than both groups. MicroRNA-125a was associated with VLDL subfractions and small LDL particles. Other microRNAs (96, 132, 191, 451) showed associations with certain LDL subfractions.

Conclusions

In patients with RA, elevated levels of VLDL particles have been observed, while LDL levels remain similar to controls. The notable association of microRNA-125a with the metabolism of both VLDL and LDL in RA patients suggests its involvement in lipid regulation. This could point to microRNA-125a as a promising therapeutic target to address the increased cardiovascular risks of RA.