miR-135b levels in the peripheral blood serve as a marker associated with acute ischemic stroke

Abstract

The protective role of microRNA (miR)-135b in cerebral neurons has been previously identified. However, to the best of our knowledge, the involvement of miR-135b in acute ischemic stroke has yet to be elucidated. The present study aimed to investigate the expression profile of miR-135b in peripheral blood obtained from patients with acute ischemic stroke. A total of 76 patients with acute ischemic stroke were selected as the case group, which included 33 cases of aorta atheromatous plague, 19 cases of cardioembolism, 16 cases of small arterial occlusion and 8 cases with unknown causes. In addition, 60 healthy subjects were selected as the control group. Reverse transcription-quantitative PCR was used to measure the expression of miR-135b in the peripheral blood of the patients. The National Institutes of Health Stroke Scale (NIHSS) score was used to evaluate the severity of acute ischemic stroke. The relationship between miR-135b levels and acute stroke was subsequently analyzed. The expression of miR-135b in the peripheral blood of the case group was found to be significantly higher compared with that in the control group. By contrast, the expression levels of miR-135b in the case group did not differ significantly between the different etiology types of acute ischemic stroke. In addition, a significant positive correlation was observed between levels of miR-135b expression and NIHSS scores. Further analysis demonstrated that hypertension, hyperglycemia, platelet count, international normalized ratio and miR-135b were risk factors for acute ischemic stroke. Based on bioinformatics analysis, a conserved binding site for miR-135b was identified in the 3'-untranslated region of the transient receptor potential cation channel subfamily C member 6 (TRPC6). Dual luciferase reporter and western blot analysis showed that TRPC6 was a target gene of miR-135b. In conclusion, data from the present study suggest that elevated expression of miR-135b in the peripheral blood of patients with acute ischemic stroke is closely associated with disease severity.

Circulating MicroRNAs and Extracellular Vesicle-Derived MicroRNAs as Predictors of Functional Recovery in Ischemic Stroke Patients: A Systematic Review and Meta-Analysis

“…Correlation coefficients (Spearman, Kendall, and Pearson) between miRNA expressions and neurological endpoints were analyzed for 68 of the 72 biomarkers, involving in total 5451 IS patients, 81 TIA patients, and 3700 controls. The expression of 10 miRNAs (miR-195, -497, -21, -132, -29b, -24, -409-3p, -135b, -185, and -424) were very strongly correlated with neurological outcome [50,51,58,69,75,80,83,87], whereas the levels of 25 miRNAs had a strong correlation with stroke recovery scores. No statistical significance was obtained for 17 miRNAs.…”

“…However, in five studies, miRNA quantification was made in both the acute and chronic phases. The following miRNAs have been identified as stroke recovery biomarkers, with prognostic values evaluated at different time points: miR-210 was evaluated at 3 days, 7 days, and 14 days [102]; miR-411-5p was isolated from serum before rt-PA, 24 h after rt-PA, and 3 months (90 days) after stroke onset [53]; miR-497 was assessed from serum at admission and at discharge [79]; miR-135b was isolated from serum within 24 h and at day 14 after stroke onset [83]; and MiR-503 from serum was quantified within 72 h + 3 months [86].…”

Novel Biomarkers of Atherosclerotic Vascular Disease—Latest Insights in the Research Field

“…Special attention has also been paid in recent studies to noncoding RNAs (ncRNAs) which are involved in several processes such as atherosclerosis, angiogenesis, neuroinflammation, or apoptosis, but their clinical applicability is currently limited [103][104][105]. Zhao et al [103] concluded that ncRNAs are potential biomarkers for early diagnosis of ischemic stroke similar to miR-107 and miR-135b [106,107]. Type 2 diabetes mellitus is a risk factor for the development and progression of CAD, changes in serum levels of various miRNAs can be used for diagnosis and prognostic stratification [108][109][110].…”

Novel Mechanistic Insights and Potential Therapeutic Impact of TRPC6 in Neurovascular Coupling and Ischemic Stroke

“…It is reported that activating TRPC6 in a rat model of cerebral ischemia was shown to prevent neuronal death, whereas blocking TRPC6 enhanced sensitivity to ischemia [ 22 ]. One mechanism is that in patients treated for acute ischemic stroke, elevated expression levels in the peripheral blood of miR-488 and miR-135b, which were shown to target the TRPC6 gene, were identified as risk factors or associated with disease severity [ 23 , 24 ]. Here, we assess the evidence for and against the beneficial consequence of TRPC6 activation in ischemic stroke, its cell-specific roles in the brain, what is known about the involvement of TRPC6 in neurovascular coupling, and the potential therapeutic options for targeting TRPC6.…”