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Plasma Exosomal Proteomic Analysis between Moyamoya Disease and Intracranial Atherosclerotic Disease.

ABSTRACT: Moyamoya disease (MMD) and atherosclerosis (ICAD) are both common causes of chronic intracranial vascular occlusion. Surgical revascularization is the preferred procedure for MMD but is not recommended for ICAD, and may be related to vascular reserve capacity, however, the precise reason is not fully understood. Previous studies showed exosomes could regulate revascularization, so we hypothesize plasma exosomal proteins play critical roles in MMD during revascularization. Quantitative proteomics technique and bioinformatics method were used to identify potential key plasma exosomal proteins for revascularization in MMD.

ORGANISM(S): Homo Sapiens

SUBMITTER: Jianfeng Liang

PROVIDER: PXD033463 | iProX | Wed Apr 27 00:00:00 BST 2022

REPOSITORIES: iProX

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Project description:Purpose: This study aimed to explore the differential expression profiles of exosomal lncRNAs and evaluated their potential utility in the accurate diagnosis of LAA stroke. Methods: LncRNA profiles of exosomes in large artery atherosclerosis stroke and controls were generated by high-throughput sequencing. The sequence reads that passed quality filters were analyzed at the transcript isoform level with Hisat2, Trapnell, STAR. qRT–PCR validation was performed using TaqMan and SYBR Green assays. Results: A total of 1020 differentially expressed lncRNAs were identified in LAA stroke patients. GO and KEGG pathway analyses indicated that their target genes are involved in atherosclerosis-related pathways, including inflammation, cell adhesion, and cell migration. 8 exosomal lncRNAs were confirmed with qRT–PCR.The result showed that the expression trend of differential expressed lncRNAs in validation was consistent with RNA-seq.Conclusion: Our study showed the differential expression of lncRNAs in plasma exosomes and presented related diagnostic potential for LAA stroke for the first time. The results suggested that exosomal lncRNA could be potential diagnostic tools in LAA stroke. Circular RNAs (circRNAs), novel endogenous noncoding RNAs, play diverse roles in ischemic stroke. Recently, the abundance and stability of circRNAs in exosomes have been identified. However, a comprehensive analysis of exosomal circRNAs in large artery atherosclerotic (LAA) stroke has not yet been reported. We performed RNA sequencing (RNA-Seq) to comprehensively identify differentially expressed exosomal circRNAs in five paired LAA and normal controls. RNA-Seq identified a total of 462 circRNAs in peripheral exosomes; there were 25 differentially expressed circRNAs among them. Additionally, circRNA competing endogenous RNA (ceRNA) network and translatable analysis revealed the potential functions of the exosomal circRNAs in LAA progression. Two ceRNA pathways involving 5 circRNAs, 2 miRNAs, and 3 mRNAs were confirmed by qRT-PCR. In the validation cohort, receiver operating characteristic (ROC) curve analysis identified two circRNAs as possible novel biomarkers, and a logistic model combining two and four circRNAs increased the area under the curve compared with the individual circRNAs.

Dataset Information

Plasma Exosomal Proteomic Analysis between Moyamoya Disease and Intracranial Atherosclerotic Disease.

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