Abstract
Ischemic stroke induces profound effects on the peripheral immune system, which may participate the infectious complications. However, the exact function and mechanism of immune reaction in stroke development are not well-elucidated. Recently, several long non-coding RNAs (LncRNAs) are reported to affect ischemic stroke process, especially the immunological response after stroke. In the present study, we investigated the profile of LncRNAs in human ischemic stroke during the transition from the acute to subacute stage, when the state of the peripheral immune system changes from activation to systemic immunosuppression. In this study, we analyzed the RNA-sequencing (RNA-seq) datasets obtained at two time points (24 h and 7 days) from the peripheral blood mononuclear cells of ischemic patients. Vascular risk factor-matched healthy adults were enrolled as controls. A total of 3,009 LncRNAs and 3,982 mRNAs were identified as differentially expressed 24 h after stroke. Furthermore, 2,034 LncRNAs and 1,641 mRNAs were detected to be differentially expressed on day 7. Bioinformatics analyses, including GO, KEGG pathway enrichment analysis, and network analysis, were performed for the identified dysregulated genes. Our study reveals that ischemic stroke can influence the expression of LncRNAs and mRNAs in the peripheral blood at both the acute and subacute stages; the level of LncRNAs in the antigen processing and presentation pathway was clearly upregulated at 24 h and had recovered to normal levels on day 7 after stroke. Moreover, inflammatory mediator regulation of TRP channels and GABAergic synapses were two specifically downregulated pathways on day 7 after stroke. Our findings provide a valuable resource for further study of the role of LncRNAs in peripheral immune system changes following ischemic stroke.
Highlights
Acute ischemic stroke (IS) is a major cause of mortality and disability worldwide, and the incidence is increasing [1]
We enrolled 5 patients (10 samples) between the ages of 50 and 75 years with first-ever acute ischemic stroke defined as acute lesion on diffusionweighted image (DWI), corresponding acute neurological deficit and anterior or middle cerebral artery occlusion proved by magnetic resonance angiography (MRA), who arrived at the hospital between 4.5 to 24 h after symptom onset (Table 1)
We found that the level of long non-coding RNAs (LncRNAs) in the pathway of antigen processing and presentation
Summary
Acute ischemic stroke (IS) is a major cause of mortality and disability worldwide, and the incidence is increasing [1]. Accumulating evidence has shown that long non-coding RNAs (LncRNAs) play critical roles in the pathogenesis of rodent [2, 3] and human ischemic stroke [4]. With the development of high-throughput technologies, recent studies have revealed that many non-coding RNAs play critical roles in cellular homeostasis [5, 6]. Several LncRNAs have been shown to play roles in animal models of stroke and oxygen-glucose deprivation (OGD) cell models [2, 10]. After exposure to OGD, which mimics ischemic conditions in vitro, the expression of LncRNAs changed significantly in mouse brain microvascular endothelial cells [12]. As there is a species difference between rodents and humans, the lncRNA profile after ischemic stroke in patients definitely needs to be investigated. We used nextgeneration sequencing technology to characterize the systemic gene expression of peripheral blood mononuclear cells (PBMCs) in ischemic stroke patients
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