Ischemic Stroke and Sleep: The Linking Genetic Factors.
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ABSTRACT:
SUBMITTER: Korostovtseva L
PROVIDER: S-EPMC8555086 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Using a hitherto uncharacterized knockout mouse model of Notch 3, a Notch signaling receptor paralogue highly expressed in vascular SMCs, we uncover a striking susceptibility to ischemic stroke upon challenge. Cellular and molecular analyses of vascular SMCs derived from these animals associate Notch 3 activity to the expression of specific gene targets, whereas genetic rescue experiments unambiguously link Notch 3 function in vessels to the ischemic phenotype. Microarray Studies. Biotinylated cRNA samples from freshly sorted brain SMCs (four Notch 3 +/- mice and five Notch 3 -/- mice) were fragmented before hybridization (15 ug each) onto mouse 430 2.0 Affymetrix chips. The chips were washed, stained by using strepavidin-phycoerytrin, and scanned the next day as described in ref. 24. For data normalization, all probe sets were scaled to a target intensity of 150. Microarray data analysis was performed by using Rosetta Resolver. All cells were from 10- to 12-week-old male mice. Gene Ontology Analyses. PANTHER software was used to define over- and underrepresented functions in the list of signature genes found by microarray analysis (25). P values were calculated by using binomial statistics.
2014-06-11 | E-GEOD-58368 | biostudies-arrayexpress
Project description:Using a hitherto uncharacterized knockout mouse model of Notch 3, a Notch signaling receptor paralogue highly expressed in vascular SMCs, we uncover a striking susceptibility to ischemic stroke upon challenge. Cellular and molecular analyses of vascular SMCs derived from these animals associate Notch 3 activity to the expression of specific gene targets, whereas genetic rescue experiments unambiguously link Notch 3 function in vessels to the ischemic phenotype.
2014-06-11 | GSE58368 | GEO
Project description:Understanding the genetic risk factors for stroke is an essential step to decipher the underlying mechanisms, facilitate the identification of novel therapeutic targets, and optimize the design of prevention strategies. A very small proportion of strokes are attributable to monogenic conditions, the vast majority being multifactorial, with multiple genetic and environmental risk factors of small effect size. Genome-wide association studies and large international consortia have been instrumental in finding genetic risk factors for stroke. While initial studies identified risk loci for specific stroke subtypes, more recent studies also revealed loci associated with all stroke and all ischemic stroke. Risk loci for ischemic stroke and its subtypes have been implicated in atrial fibrillation (PITX2 and ZFHX3), coronary artery disease (ABO, chr9p21, HDAC9, and ALDH2), blood pressure (ALDH2 and HDAC9), pericyte and smooth muscle cell development (FOXF2), coagulation (HABP2), carotid plaque formation (MMP12), and neuro-inflammation (TSPAN2). For hemorrhagic stroke, two loci (APOE and PMF1) have been identified.
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Project description:The cause of perinatal arterial ischemic stroke is unknown in most cases. We explored whether genetic polymorphisms modify the risk of perinatal arterial ischemic stroke. In a population-based case-control study of 1997-2002 births at Kaiser Permanente Northern California, we identified 13 white infants with perinatal arterial ischemic stroke. Control subjects included 86 randomly selected white infants. We genotyped polymorphisms in nine genes involved in inflammation, thrombosis, or lipid metabolism previously linked with stroke, and compared genotype frequencies in case and control individuals. We tested several polymorphisms: tumor necrosis factor-? -308, interleukin-6, lymphotoxin A, factor V Leiden, methyltetrahydrofolate reductase 1298 and 667, prothrombin 20210, and apolipoprotein E ?2 and ?4 alleles. Patients with perinatal arterial ischemic stroke were more likely than control subjects to demonstrate at least one apolipoprotein E ?4 allele (54% vs 25%, P = 0.03). More patients with perinatal arterial ischemic stroke carried two ?4 alleles than did control subjects (15% vs 2%, P = 0.09), although this finding lacked statistical significance. Proinflammatory and prothrombotic polymorphisms were not associated with perinatal arterial ischemic stroke. The apolipoprotein E polymorphism may confer genetic susceptibility for perinatal arterial ischemic stroke. Larger population-based studies are required to confirm this finding.
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Project description:The literature indicates that obstructive sleep apnea (OSA) increases the risk of ischemic stroke. However, the causal relationship between OSA and ischemic stroke is not well established. This study examined whether preexisting OSA symptoms affect the onset of acute ischemic stroke.We investigated consecutive patients who were admitted with acute ischemic stroke, using a standardized protocol including the Berlin Questionnaire on symptoms of OSA prior to stroke. The collected stroke data included the time of the stroke onset, risk factors, and etiologic subtypes. The association between preceding OSA symptoms and wake-up stroke (WUS) was assessed using multivariate logistic regression analysis.We identified 260 subjects with acute ischemic strokes with a definite onset time, of which 25.8% were WUS. The presence of preexisting witnessed or self-recognized sleep apnea was the only risk factor for WUS (adjusted odds ratio=2.055, 95% confidence interval=1.035-4.083, p=0.040).Preexisting symptoms suggestive of OSA were associated with the occurrence of WUS. This suggests that OSA contributes to ischemic stroke not only as a predisposing risk factor but also as a triggering factor. Treating OSA might therefore be beneficial in preventing stroke, particularly that occurring during sleep.
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Project description:Alzheimer's disease (AD) and ischemic stroke (IS) are common neurological disorders, and the comorbidity of these two brain diseases is often seen. Although AD and IS were regarded as two distinct disease entities, in terms of different etiologies and clinical presentation, recent genome-wide association studies (GWASs) revealed that there were common risk genes between AD and IS, indicating common molecular pathways and their common pathophysiology. In this review, we summarize AD and IS risk single nucleotide polymorphisms (SNPs) and their representative genes from the GWAS Catalog database, and find thirteen common risk genes, but no common risk SNPs. Furthermore, the common molecular pathways associated with these risk gene products are summarized from the GeneCards database and clustered into inflammation and immunity, G protein-coupled receptor, and signal transduction. At least seven of these thirteen genes can be regulated by 23 microRNAs identified from the TargetScan database. Taken together, the imbalance of these molecular pathways may give rise to these two common brain disorders. This review sheds light on the pathogenesis of comorbidity of AD and IS, and provides molecular targets for disease prevention, manipulation, and brain health maintenance.
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Project description:BackgroundObstructive sleep apnea (OSA) has been associated with cardiac abnormalities. Whether any cardiac dysfunction is present in ischemic stroke patients with OSA is not known. The purpose of this study was to compare echocardiographic findings in ischemic stroke patients with and without OSA.MethodsNocturnal polysomnography was performed on 28 ischemic stroke subjects within 7 days of symptom onset. OSA was defined as an apnea-hypopnea index of ≥10. Echocardiographic variables were compared between the OSA and non OSA groups using Wilcoxon signed-rank, chi-square, or Fisher's exact tests.ResultsThe 14 (50%) subjects with OSA had comparable cardiac function and structure to those without OSA (n=14). Left ventricular (LV) mass index, LV ejection fraction, LV diastolic function, left atrial area, and right ventricular systolic function were not different between groups. Ischemic stroke subjects, regardless of their OSA status, had LV diastolic dysfunction with preserved systolic function.ConclusionsSubjects with and without OSA, based on polysomnography in the first 7 days after stroke, have comparable right and left ventricular function.
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