Dataset Information

Circulating Extracellular Vesicle Proteins and MicroRNA Profiles in Subcortical and Cortical-Subcortical Ischaemic Stroke.

ABSTRACT: In order to investigate the role of circulating extracellular vesicles (EVs), proteins, and microRNAs as damage and repair markers in ischaemic stroke depending on its topography, subcortical (SC), and cortical-subcortical (CSC) involvement, we quantified the total amount of EVs using an enzyme-linked immunosorbent assay technique and analysed their global protein content using proteomics. We also employed a polymerase chain reaction to evaluate the circulating microRNA profile. The study included 81 patients with ischaemic stroke (26 SC and 55 CSC) and 22 healthy controls (HCs). No differences were found in circulating EV levels between the SC, CSC, and HC groups. We detected the specific expression of C1QA and Casp14 in the EVs of patients with CSC ischaemic stroke and the specific expression of ANXA2 in the EVs of patients with SC involvement. Patients with CSC ischaemic stroke showed a lower expression of miR-15a, miR-424, miR-100, and miR-339 compared with those with SC ischaemic stroke, and the levels of miR-339, miR-100, miR-199a, miR-369a, miR-424, and miR-15a were lower than those of the HCs. Circulating EV proteins and microRNAs from patients with CSC ischaemic stroke could be considered markers of neurite outgrowth, neurogenesis, inflammation process, and atherosclerosis. On the other hand, EV proteins and microRNAs from patients with SC ischaemic stroke might be markers of an anti-inflammatory process and blood-brain barrier disruption reduction.

SUBMITTER: Otero-Ortega L

PROVIDER: S-EPMC8301391 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Circulating Extracellular Vesicle Proteins and MicroRNA Profiles in Subcortical and Cortical-Subcortical Ischaemic Stroke.

Otero-Ortega Laura L Alonso-López Elisa E Pérez-Mato María M Laso-García Fernando F Gómez-de Frutos Mari Carmen MC Diekhorst Luke L García-Bermejo María Laura ML Conde-Moreno Elisa E Fuentes Blanca B de Leciñana María Alonso MA Bravo Susana B SB Díez-Tejedor Exuperio E Gutiérrez-Fernández María M

Biomedicines 20210707 7

In order to investigate the role of circulating extracellular vesicles (EVs), proteins, and microRNAs as damage and repair markers in ischaemic stroke depending on its topography, subcortical (SC), and cortical-subcortical (CSC) involvement, we quantified the total amount of EVs using an enzyme-linked immunosorbent assay technique and analysed their global protein content using proteomics. We also employed a polymerase chain reaction to evaluate the circulating microRNA profile. The study includ ...[more]

PMID: 34356850

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Project description:Background and purposeThis study aimed to evaluate whether extracellular-vesicle-incorporated microRNAs (miRNAs) are potential biomarkers for cancer-related stroke.MethodsThis cohort study compared patients with active cancer who had embolic stroke of unknown sources (cancer-stroke group) with patients with only cancer, patients with only stroke, and healthy individuals (control groups). The expression profiles of miRNAs encapsulated in plasma exosomes and microvesicles were evaluated using microarray and validated using quantitative real-time polymerase chain reaction. The XENO-QTM miRNA assay technology was used to determine the absolute copy numbers of individual miRNAs in an external validation cohort.ResultsThis study recruited 220 patients, of which 45 had cancer-stroke, 76 were healthy controls, 39 were cancer controls, and 60 were stroke controls. Three miRNAs (miR-205-5p, miR-645, and miR-646) were specifically incorporated into microvesicles in patients with cancer-related stroke, cancer controls, and stroke controls. The area under the receiver operating characteristic curves of these three miRNAs were 0.7692-0.8510 for the differentiation of patients with cancer-stroke from cancer-controls and 0.8077-0.8846 for the differentiation of patients with cancer-stroke from stroke controls. The levels of several miRNAs were elevated in the plasma exosomes of patients with cancer, but were lower than those in plasma microvesicles. An in vivo study showed that systemic injection of miR-205-5p promoted the development of arterial thrombosis and elevation of D-dimer levels.ConclusionStroke due to cancer-related coagulopathy was associated with deregulated expression of miRNAs, particularly microvesicle-incorporated miR-205-5p, miR-645, and miR-646. Further prospective studies of extracellular-vesicle-incorporated miRNAs are required to confirm the diagnostic role of miRNAs in patients with stroke and to screen the roles of miRNAs in patients with cancer.

Project description:Subcortical ischemic stroke can lead to persistent structural changes in the cerebral cortex. The evolution of cortical structural changes after subcortical stroke is largely unknown, as are their relations with motor recovery, lesion location, and early impairment of specific subsets of fibers in the corticospinal tract (CST). In this observational study, cortical structural changes were compared between 181 chronic patients with subcortical stroke involving the motor pathway and 113 healthy controls. The impacts of acute lesion location and early impairments of specific CSTs on cortical structural changes were investigated in the patients by combining voxel-based correlation analysis with an association study that compared CST damage and cortical structural changes. Longitudinal patterns of cortical structural change were explored in a group of 81 patients with subcortical stroke using a linear mixed-effects model. In the cross-sectional analyses, patients with partial recovery showed more significant reductions in cortical thickness, surface area, or gray matter volume in the sensorimotor cortex, cingulate gyrus, and gyrus rectus than did patients with complete recovery; however, patients with complete recovery demonstrated more significant increases in the cortical structural measures in frontal, temporal, and occipital regions than did patients with partial recovery. Voxel-based correlation analysis in these patients showed that acute stroke lesions involving the CST fibers originating from the primary motor cortex were associated with cortical thickness reductions in the ipsilesional motor cortex in the chronic stage. Acute stroke lesions in the putamen were correlated with increased surface area in the temporal pole in the chronic stage. The early impairment of the CST fibers originating from the primary sensory area was associated with increased cortical thickness in the occipital cortex. In the longitudinal analyses, patients with partial recovery showed gradually reduced cortical thickness, surface area, and gray matter volume in brain regions with significant structural damage in the chronic stage. Patients with complete recovery demonstrated gradually increasing cortical thickness, surface area, and gray-matter volume in the frontal, temporal, and occipital regions. The directions of slow structural changes in the frontal, occipital, and cingulate cortices were completely different between patients with partial and complete recovery. Complex cortical structural changes and their dynamic evolution patterns were different, even contrasting, in patients with partial and complete recovery, and were associated with lesion location and with impairment of specific CST fiber subsets.

Dataset Information

Circulating Extracellular Vesicle Proteins and MicroRNA Profiles in Subcortical and Cortical-Subcortical Ischaemic Stroke.

Publications

Circulating Extracellular Vesicle Proteins and MicroRNA Profiles in Subcortical and Cortical-Subcortical Ischaemic Stroke.

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