Differential expression of circulating exosomal microRNAs in refractory intracranial atherosclerosis associated with antiangiogenesis

Abstract

Intracranial atherosclerotic disease (ICAD) is a common cause of stroke with high rates of ischemic recurrence. We aimed to investigate the role of circulating exosomal microRNAs (e-miRNAs) in recurrent ischemic events in ICAD. Consecutive patients with severe ICAD undergoing intensive medical management (IMM) were prospectively enrolled. Those with recurrent ischemic events despite IMM during 6-month follow up were algorithmically matched to IMM responders. Baseline blood e-miRNA expression levels of the matched patients were measured using next generation sequencing. A total of 122 e-miRNAs were isolated from blood samples of 10 non-responders and 11 responders. Thirteen e-miRNAs predicted IMM failure with 90% sensitivity and 100% specificity. Ingenuity pathway analysis (IPA) determined 10 of the 13 e-miRNAs were significantly associated with angiogenesis-related biological functions (p < 0.025) and angiogenic factors that have been associated with recurrent ischemic events in ICAD. These e-miRNAs included miR-122-5p, miR-192-5p, miR-27b-3p, miR-16-5p, miR-486-5p, miR-30c-5p, miR-10b-5p, miR-10a-5p, miR-101-3p, and miR-24-3p. As predicted by IPA, the specific expression profiles of these 10 e-miRNAs in non-responders had a net result of inhibition of the angiogenesis-related functions and up expression of the antiangiogenic factors. This study revealed distinct expression profiles of circulating e-miRNAs in refractory ICAD, suggesting an antiangiogenic mechanism underlying IMM failure.

MiR-10a, 27a, 34b/c, and 300 Polymorphisms are Associated with Ischemic Stroke Susceptibility and Post-Stroke Mortality

“…down-regulation or loss of miR-10a has promoted endothelial inflammation, and it is affected atherosclerosis that is the primary cause of ischemic stroke [16,82]. Also, in Wei et al, the miR-34b/c rs4938723 C allele, compared with the T allele, showed to decrease the transcriptional activity of the miR-34b/c promoter, and this study demonstrated that the miR-34b/c rs4938723 C allele affected the down-regulation [83].…”

“…In Li et al, the miR-10a rs389783 T allele, compared with the A allele, showed decreased expression levels of the mature miR-10a, and it was connected that the miR-10a rs389783 T allele affects the down-regulation [55]. In Kumar et al and Jiang et al, down-regulation or loss of miR-10a has promoted endothelial inflammation, and it is affected atherosclerosis that is the primary cause of ischemic stroke [16,82]. Also, in Wei et al, the miR-34b/c rs4938723 C allele, compared with the T allele, showed to decrease the transcriptional activity of the miR-34b/c promoter, and this study demonstrated that the miR-34b/c rs4938723 C allele affected the down-regulation [83].…”

Circulating Exosomal miRNAs as Novel Biomarkers for Stable Coronary Artery Disease

“…However, few reports have focused on the value of circulating exosomal miRNAs as biomarkers for SCAD. In this study, eight miRNAs, miR-192-5p [ 21 ], miR-148b-3p [ 22 ], miR-125a-3p [ 23 ], miR-942-5p [ 24 ], miR-149-5p [ 25 ], miR-32-5p [ 26 ], miR-144-3p [ 27 ], and miR-142-5p [ 28 ], which have been reported to be involved in the development of cardiovascular diseases were selected. The expression levels of these miRNAs in the circulating exosomes from the control and SCAD groups were detected by qPCR.…”

Exosomes in atherosclerosis: performers, bystanders, biomarkers, and therapeutic targets

“…Jiang et al found that a specific circulating exosomal miRNA signature ( miR-122-5p , miR-27b-3p , miR-101-3p , etc.) is a novel biomarker predicting recurrent ischemic events in intracranial atherosclerotic disease 195 . Additionally, release of exosomal miR-92a-3p from endothelial cells is associated with atherogenic conditions and could serve as a potential diagnostic biomarker 196 .…”