Progression of asymptomatic carotid artery stenosis (ACAS) in patients with >50% luminal narrowing is considered a potential risk factor for ischemic stroke; however, subclinical molecular biomarkers of ACAS progression are lacking. Recent studies suggest a regulatory function for several microRNAs (miRNAs) on the evolution of carotid plaque, but its role in ACAS progression is mostly unknown. The aim of this study was to investigate a wide miRNA panel in peripheral blood exosomes from patients with ACAS to associate circulating miRNA expression profiles with stenosis progression.
The study included 60 patients with ACAS carrying >50% luminal narrowing. First, miRNA expression profiles of circulating exosomes were determined by Affymetrix microarrays from plasma samples of 16 patients from the cohort. Second, those miRNAs among the most differentially expressed in patients with ACAS progression were quantified by real-time polymerase chain reaction in a separate replication cohort of 39 subjects within the patient sample.
The results showed that ACAS progression was associated with development of stroke. MiR-199b-3p, miR-27b-3p, miR-130a-3p, miR-221-3p, and miR-24-3p presented significant higher expression in those patients with ACAS progression.
Principal component analysis (PCA) and hierarchical clustering (HC)
from patients with asymptomatic carotid artery stenosis (ACAS).
The PCA image (A) shows a different distribution for noncoding RNA expression profiles of samples from patients with ACAS progression (pink spheres) compared with that in patients without progression (green spheres). The HC representation (B) shows different miRNA expression profiles in patients with asymptomatic carotid artery stenosis progression (rows from the pink bar) compared with patients without progression (rows from the green bar; P<0.05). Red areas represent miRNAs that are overexpressed and blue those that are lower expressed on each row sample.
This study supports that specific circulating miRNA expression profiles could provide a new tool that complements the monitoring of ACAS progression, improving therapeutic approaches to prevent ischemic stroke.