Associations of circulating cell-free micro-RNA with vasculopathy and vascular events in SLE patients

Background/Purpose: MicroRNAs (miRNAs) are small noncoding RNAs that modulate protein translation and regulate numerous immunologic and inflammatory pathways. Certain miRNA profiles have been associated with several diseases, including atherosclerosis. Patients with systemic lupus erythematosus (SLE) are known to have a high prevalence of atherosclerosis and a recent study has shown that circulating miRNAs are systematically altered in SLE. Therefore, our objective was to investigate the association between markers of atherosclerosis and cell-free circulating microRNAs in patients with systemic lupus erythematosus. Methods: 120 SLE patients were screened for atherosclerosis by means of cardiac CT demonstrating coronary artery calcification (CAC) and carotid ultrasound visualizing intima-media thickness (IMT) and plaque. Atherosclerosis was defined as either CAC > 99U, carotid IMT>1.00mm and/or carotid plaque. Total RNA was purified from plasma, and 46 specific miRNAs were determined using quantitative real time PCR on a dynamic microfluidic array. Patients with atherosclerosis were compared to those without in terms of expression of cell-free circulating miRNAs. Results: Six miRNAs were expressed differently in plasma from SLE patients with atherosclerosis compared to those without. The expression of miR- 125b, miR-29b-3p, miR-375, miR-101, miR- 122-5p and miR-20a were all decreased in SLE patients with atherosclerosis. Unsupervised hierarchical clustering identified miRNA profiles (an 8-miRNA signature) that differentiated a group of SLE patients from the rest. This patient group (n=16) had significantly increased frequencies of recorded venous thrombotic events (p=0.045), a higher prevalence of beta2- glycoprotein 1 IgG antibodies (p=0.029), and significantly lower platelet counts (p=0.024). Conclusion: Six circulating miRNAs are for the first time shown to be associated with atherosclerosis in a cross-sectional SLE cohort. Furthermore, an 8-miRNA signature was associated with the phenotype of the antiphospholipid syndrome with the patients having a history of venous thrombotic events, beta2-glycoprotein 1 antibodies and lower platelet counts. The findings warrant further prospective studies of the putative association between specific circulating miRNAs and vasculopathy in SLE patients.