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The X-chromosome has a different pattern of gene expression in women compared with men with ischemic stroke.

ABSTRACT: Differences in ischemic stroke between men and women have been mainly attributed to hormonal effects. However, sex differences in immune response to ischemia may exist. We hypothesized that differential expression of X-chromosome genes in blood immune cells contribute to differences between men and women with ischemic stroke.RNA levels of 683 X-chromosome genes were measured on Affymetrix U133 Plus2.0 microarrays. Blood samples from patients with ischemic stroke were obtained at ? 3 hours, 5 hours, and 24 hours (n=61; 183 samples) after onset and compared with control subjects without symptomatic vascular diseases (n=109). Sex difference in X-chromosome gene expression was determined using analysis of covariance (false discovery rate ? 0.05, fold change ? 1.2).At ? 3, 5, and 24 hours after stroke, there were 37, 140, and 61 X-chromosome genes, respectively, that changed in women; and 23, 18, and 31 X-chromosome genes that changed in men. Female-specific genes were associated with post-translational modification, small-molecule biochemistry, and cell-cell signaling. Male-specific genes were associated with cellular movement, development, cell-trafficking, and cell death. Altered sex specific X-chromosome gene expression occurred in 2 genes known to be associated with human stroke, including galactosidase A and IDS, mutations of which result in Fabry disease and Hunter syndrome, respectively.There are differences in X-chromosome gene expression between men and women with ischemic stroke. Future studies are needed to decipher whether these differences are associated with sexually dimorphic immune response, repair or other mechanisms after stroke, or whether some of them represent risk determinants.

SUBMITTER: Stamova B

PROVIDER: S-EPMC3938328 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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The X-chromosome has a different pattern of gene expression in women compared with men with ischemic stroke.

Stamova Boryana B Tian Yingfang Y Jickling Glen G Bushnell Cheryl C Zhan Xinhua X Liu Dazhi D Ander Bradley P BP Verro Piero P Patel Vihar V Pevec William C WC Hedayati Nasim N Dawson David L DL Jauch Edward C EC Pancioli Arthur A Broderick Joseph P JP Sharp Frank R FR

Stroke 20111103 2

<h4>Background and purpose</h4>Differences in ischemic stroke between men and women have been mainly attributed to hormonal effects. However, sex differences in immune response to ischemia may exist. We hypothesized that differential expression of X-chromosome genes in blood immune cells contribute to differences between men and women with ischemic stroke.<h4>Methods</h4>RNA levels of 683 X-chromosome genes were measured on Affymetrix U133 Plus2.0 microarrays. Blood samples from patients with is ...[more]

PMID: 22052522

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Project description:Background and Purpose- Clinical deficits from ischemic stroke are more severe in women, but the pathophysiological basis of this sex difference is unknown. Sex differences in core and penumbral volumes and their relation to outcome were assessed in this substudy of the DEFUSE 3 clinical trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke). Methods- DEFUSE 3 randomized patients to thrombectomy or medical management who presented 6 to 16 hours from last known well with proximal middle cerebral artery or internal carotid artery occlusion and had target core and perfusion mismatch volumes on computed tomography or magnetic resonance imaging. Using univariate and adjusted regression models, the effect of sex was assessed on prerandomization measures of core, perfusion, and mismatch volumes and hypoperfusion intensity ratio, and on core volume growth using 24-hour scans. Results- All patients were included in the analysis (n=182) with 90 men and 92 women. There was no sex difference in the site of baseline arterial occlusion. Adjusted by age, baseline National Institutes of Health Stroke Scale, baseline modified Rankin Scale score, time to randomization, and imaging modality, women had smaller core, hypoperfusion, and penumbral volumes than men. Median (interquartile range) volumes for core were 8.0 mL (1.9-18.4) in women versus 12.6 mL (2.7-29.6) in men, for Tmax>6 seconds 89.0 mL (63.8-131.7) versus 133.9 mL (87.0-175.4), and for mismatch 82.1mL (53.8-112.8) versus 108.2 (64.1-149.2). The hypoperfusion intensity ratio was lower in women, 0.31 (0.15-0.46) versus 0.39 (0.26-0.57), P=0.006, indicating better collateral circulation, which was consistent with the observed slower ischemic core growth than men within the medical group (P=0.003). Conclusions- In the large vessel ischemic stroke cohort selected for DEFUSE 3, women had imaging evidence of better collateral circulation, smaller baseline core volumes, and slower ischemic core growth. These observations suggest sex differences in hemodynamic and temporal features of anterior circulation large artery occlusions. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT02586415.

Project description:Pre-existing diabetes mellitus worsens brain functionality in ischemic stroke. We have previously shown that type 2 diabetic rats exhibit enhanced dysfunctional cerebral neovascularization and when these rats are subjected to cerebral ischemic reperfusion injury develop hemorrhagic transformation and greater neurological deficits. However, our knowledge of vascular and functional plasticity during the recovery phase of diabetic stroke is limited. This study tested the hypothesis that vascular repair is impaired in the poststroke period in diabetes mellitus, and this is associated with poor sensorimotor and cognitive function. We further hypothesized that glycemic control prevents impaired vascularization and improves functional outcome in diabetes mellitus.Vascularization was assessed in the ipsilateral and contralateral hemispheres in control, diabetes mellitus and diabetes mellitus plus metformin groups 14 days after ischemic reperfusion injury, as well as in respective sham controls. Three-dimensional reconstruction of the fluorescein isothiocyanate (FITC)-stained vasculature was achieved by confocal microscopy, and stereological parameters, including vascular volume and surface area, were measured. Astrogliosis was determined by glial fibrillary acidic protein staining. The relative rates of sensorimotor recovery, cognitive decline, and spontaneous activity were assessed.Vascular density in the peri-infarct area was significantly reduced in diabetes mellitus, whereas there was reparative neovascularization in control rats. Astroglial swelling and reactivity were more pronounced in diabetic stroke compared with control stroke. Diabetes mellitus blunted sensorimotor recovery and also exacerbated anxiety-like symptoms and cognitive deficits. Glycemic control started after stroke partially prevented these changes.Diabetes mellitus impairs poststroke reparative neovascularization and impedes the recovery. Glycemic control after stroke can improve neurovascular repair and improve functional outcome.

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The X-chromosome has a different pattern of gene expression in women compared with men with ischemic stroke.

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The X-chromosome has a different pattern of gene expression in women compared with men with ischemic stroke.

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