Altered Expression of Specific MicroRNAs in Plasma of Aneurysmal Subarachnoid Hemorrhage Patients.

Lina Zheng,Yuehua Pu,Xin Zhang,Liping Liu

doi:10.3389/fneur.2022.842888

Abstract

BackgroundAneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening condition with high disability and mortality. MicroRNAs (miRNAs) are reported to play a modulating role in aSAH. We investigated specific plasma microRNAs (miRNAs) associated with aSAH and gained comprehensive insight into its pathological mechanisms.MethodsThis is a prospective case–control study. We used a two-stage approach, with primary screening and ensuing two-step validation stages. Significantly differentially expressed plasma miRNAs between aSAH patients and neurologically healthy controls were initially screened by microarray analysis. These miRNAs were then validated in two groups of independent cohorts using reverse transcription quantitative real-time polymerase chain reaction assays. Functional annotation of these miRNA targets was performed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses.ResultsIn the primary screening stage, 14 miRNAs were identified as differentially expressed at a significance level of P < 0.05 and fold change >2 between 5 aSAH patients and 5 neurologically healthy controls. In the two validation steps (20 patients vs. 20 control; 40 patients vs. 30 controls), miR-23b-3p, miR-590-5p, miR-20b-5p, miR-142-3p, and miR-29b-3p were found to be significantly down-regulated in patients with aSAH compared with controls. Through these 5 miRNAs, we obtained 32 overlapping target genes, including TGM2, EREG, EDN1, and COL4A1, in three databases that may affect the progression of aSAH. The results of functional annotation revealed mechanisms mainly related to inflammation, smooth muscle cell proliferation and cell adhesion, potentially contributing to the occurrence of aSAH.ConclusionWe demonstrate that specific miRNAs in plasma, including miR-23b-3p, miR-590-5p, miR-20b-5p, miR-142-3p, and miR-29b-3p, are significantly down-regulated in aSAH patients and may play a modulating role in its progression.

Highlights

Aneurysmal subarachnoid hemorrhage is a life-threatening condition with high disability and mortality worldwide, accounting for 5–10% of stroke [1]
There were no significant differences between the risk factors between aSAH patients and controls in each case–control cohort
Among the five miRNAs screened and validated in our study, it had been previously reported that miRNA-29b and miRNA-23b-3p are differentially expressed in intracranial aneurysm tissues compared with normal tissues [5]; in addition, miR-20b-5p might affect the occurrence and development of intracranial aneurysms by regulating actin cytoskeleton biogenesis [13]. miR-23b was found to result in an impaired inhibitory effect on inflammatory cytokine expression and to be closely related to the inflammatory response

Summary

Introduction

Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening condition with high disability and mortality worldwide, accounting for 5–10% of stroke [1]. Current diagnostic methods mainly depend on digital subtraction angiography (DSA). MicroRNAs in Aneurysmal Subarachnoid Hemorrhage may occur in the presence of vasospasm or thrombosis in ruptured aneurysms. DSA is an invasive operation with underlying risks. Biomarkers based on the pathophysiology of ruptured aneurysms that distinguish patients with aSAH from a healthy population are urgently needed. Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening condition with high disability and mortality. MicroRNAs (miRNAs) are reported to play a modulating role in aSAH. We investigated specific plasma microRNAs (miRNAs) associated with aSAH and gained comprehensive insight into its pathological mechanisms

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