Circulating Exosomal miRNAs as Novel Biomarkers Perform Superior Diagnostic Efficiency Compared With Plasma miRNAs for Large-Artery Atherosclerosis Stroke

Abstract

Recently, exosomal miRNAs have been reported to be associated with some diseases, and these miRNAs can be used for diagnosis and treatment. However, diagnostic biomarkers of exosomal miRNAs for ischemic stroke have rarely been studied. In the present study, we aimed to identify exosomal miRNAs that are associated with large-artery atherosclerosis (LAA) stroke, the most common subtype of ischemic stroke; to further verify their diagnostic efficiency; and to obtain promising biomarkers. High-throughput sequencing was performed on samples from 10 subjects. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed on exosomes and plasma in the discovery phase (66 subjects in total) and the validation phase (520 subjects in total). We identified 5 candidate differentially expressed miRNAs (miR-369-3p, miR-493-3p, miR-379-5p, miR-1296-5p, and miR-1277-5p) in the discovery phase according to their biological functions, 4 of which (miR-369-3p, miR-493-3p, miR-379-5p, and miR-1296-5p) were confirmed in the validation phase. These four exosomal miRNAs could be used to distinguish LAA samples from small artery occlusion (SAO) samples, LAA samples from atherosclerosis (AS) samples, and LAA samples from control samples and were superior to plasma miRNAs. In addition, composite biomarkers achieved higher area under the curve (AUC) values than single biomarkers. According to our analysis, the expression levels of exosomal miR-493-3p and miR-1296-5p were negatively correlated with the National Institutes of Health Stroke Scale (NIHSS) score. The four identified exosomal miRNAs are promising biomarkers for the diagnosis of LAA stroke, and their diagnostic efficiency is superior to that of their counterparts in plasma.

microRNAs profiling of small extracellular vesicles from midbrain tissue of Parkinson’s disease

“…Exosomes derived from neural stem cells are involved in neuroinflammation, apoptosis, and inhibition of neural regeneration via an miR-219a-2-3p-dependent mechanism (Ma et al, 2019), and overexpression of miR-219a-2-3p could promote apoptosis by suppressing MDM2 expression . miR-379-5p is related to fatty acid metabolism and metabolic pathways, and plays an important role in the pathophysiology of atherosclerosis and stroke (Niu et al, 2021). However, neuron-astrocyte coupling of fatty acid metabolism is essential for neuron survival (Ioannou et al, 2019;Qi et al, 2021), and fatty acid metabolism of neurons is also of great importance.…”

Exploration of the shared gene signatures and molecular mechanisms between atherosclerosis and rheumatoid arthritis via multi-microarray data analyses

“…These and other results suggest hsa-miR-204 probably acts as a key molecule in the development of AS in RA and deserves further study. In addition, hsa-miR-377, hsa-miR-493, and hsa-miR-525-5p have been reported in either RA or AS (68)(69)(70)(71)(72)(73), and whether these miRNAs take part in the other disease is also worthy of further investigation.…”

Exosomes in brain diseases: Pathogenesis and therapeutic targets

“…miR‐1296‐5p is associated with cell adhesion molecules and plays a key role in atherosclerosis. miR‐369‐3p, miR‐493‐3p, miR‐379‐5p, and miR‐1296‐5p are promising biomarkers for the diagnosis of LAA stroke 269 . Another study reported that lnc_000048, lnc_001350, and lnc_016442 in exosomes could effectively diagnose LAA stroke.…”

“…miR‐369‐3p, miR‐493‐3p, miR‐379‐5p, and miR‐1296‐5p are promising biomarkers for the diagnosis of LAA stroke. 269 Another study reported that lnc_000048, lnc_001350, and lnc_016442 in exosomes could effectively diagnose LAA stroke. lnc_001350 and lnc_016442 significantly improved the prediction of NIHSS in the prognosis of LAA stroke.…”