Circulating microRNAs in Carotid Atherosclerosis: Complex Interplay and Possible Associations with Atherothrombotic Stroke

Atherosclerosis is a chronic inflammatory disorder which remains the main cause of cardiovascular morbidity and mortality, with carotid atherosclerosis (CA) being a major cause of ischemic stroke. Epigenetic regulation plays a significant role in CA progression and stroke, yet the impact of circulating microRNA expression, associated with atherogenesis, has not been clearly defined. We included 81 patients with moderate-severe CA (mean age 67 ± 7 years, 53% male), 42% of whom had prior ipsilateral ischemic stroke (i.e., were symptomatic). A total of 24 miRs were identified and their plasma expression levels were measured. We observed that several microRNAs were up-regulated in stroke survivors, namely miR-200c-3p (30.6 vs. 29.7, = 0.047), miR-106b-3p (31.01 vs. 30.25, = 0.004), and miR-494-5p (39 vs. 33, < 0.001), while others (miR183-3p [25.5 vs. 28.6, < 0.001], miR-126-5p [35.6 vs. 37.1, = 0.03], and miR-216-3p [12.34 vs. 16.2, < 0.001]) had lower plasma levels in symptomatic patients. In a multivariable logistic regression model for symptomatic CA, the only miRs showing statistical significance were miR-106b-5p, miR-183-3p, miR-216-3p, and miR-494-5p. Cluster analysis demonstrated differential miR expression in CA patients depending on their stroke status. Epigenetic modulation, represented as complex interplay between circulating miRs of different atherogenic potential, may play a significant role in CA development and progression. In our study, we show possible candidates for future research regarding CA and stroke.