Circulating MicroRNAs as Potential Biomarkers for Ischemic Stroke in Patients with Asymptomatic Intracranial Artery Stenosis
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE201860 | GEO | 2024/09/25
REPOSITORIES: GEO
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Project description:Circulating MicroRNAs as Potential Biomarkers for Ischemic Stroke in Patients with Asymptomatic Intracranial Artery Stenosis
| PRJNA833323 | ENA
Project description:Objective Acute ischemic stroke is a group of diseases characterized by high morbidity, high disability, high mortality, and high recurrence, and most patients are left with varying degrees of sequelae. Symptomatic intracranial atherosclerotic stenosis (sICAS) is a major cause of acute ischemic stroke pathogenesis, and its formation and progression are influenced by a combination of pathways including lipid metabolism and inflammatory response. sICAS has a high risk of clinical recurrence. Therefore, timely and effective assessment of intracranial vascular stenosis in acute ischemic stroke is particularly important for the diagnosis of sICAS, the treatment of stroke and the prevention of stroke recurrence.Method The aim of this study was to screen for unique differential proteins that are closely associated with sICAS in patients with acute ischemic stroke. Fourteen patients with acute ischemic stroke were included and divided into stenosis and control groups according to whether the intracranial vessels were stenosed or not. First, mass spectrometry was applied to all patients included using 4D Label-free proteome quantification technology to obtain the differential proteins between the two groups. Secondly, functional enrichment analysis using GO classification, KEGG pathway, Domain and other bioinformatics libraries were used to obtain differential protein-related enrichment trends. Then, the STRING (v.11.5) protein interaction network database was applied for comparison to obtain the differential protein interactions and corresponding target proteins. Finally, PRM was applied to validate the selected target proteins.Result 1096 proteins were obtained by mass spectrometry, of which the number of quantitatively comparable proteins was 991. When P value<0.05, a change in differential expression of more than 1.3 was used as the change threshold for significant up-regulation and less than 1/1.3 was used as the change threshold for significant down-regulation, resulting in a total of 46 differential proteins screened, of which 24 proteins were significantly up-regulated and 22 proteins were significantly down-regulated. In PRM experiments, five proteins involved in lipid metabolism and inflammatory response have been validated, namely A2M ,LBP, CTSG,CST3,FABP1.Conclusion By detecting the changes of these five proteins in acute ischemic stroke patients, we can provide a basis for the diagnosis of sICAS, the treatment of stroke and the prevention of stroke recurrence, and also help to promote the development of drugs for the prevention of acute ischemic stroke recurrence by combining Chinese and Western medicine.
2023-08-15 | PXD044579 |
Project description:A microarray analysis of advanced human atherosclerotic carotid artery plaques (equal or over 70% stenosis, NASCET criteria) from radiologically confirmed ipsilateral stroke patients (stroke-susceptible plaques, n=12) compared with carotid plaques collected from clinically asymptomatic patients with clear brain imaging (asymptomatic plaques, n=9) with equivalent conventional risk factors and severity of carotid stenosis.
2011-12-30 | E-MEXP-2257 | biostudies-arrayexpress
Project description:ImportanceAsymptomatic intracranial stenosis (ICS) is a frequent finding on imaging results, particularly in the assessment of acute stroke. Although the management of symptomatic ICS is informed by randomized trials, to our knowledge there are few data on the prevalence and prognosis of asymptomatic ICS in patients with stroke and transient ischemic attack (TIA).ObjectiveTo study the age-specific prevalence and prognosis of asymptomatic ICS in a population-based cohort of patients with TIA and minor stroke.Design, setting, and participantsAll patients (predominantly white) recruited to the Oxford Vascular Study (Oxfordshire, England) between March 1, 2011, and March 1, 2018, with TIA and minor ischemic stroke (National Institutes of Health Stroke Scale score, ≤3), irrespective of age, were included (n = 1579). We determined the age-specific prevalence of 50% or more asymptomatic ICS and the associated stroke risk by face-to-face follow-up to 2018 on standard medical treatment without stenting.ExposuresPatients underwent magnetic resonance angiography of the intracranial and cervicocranial arteries, computed tomography angiography if magnetic resonance angiography was contraindicated, or carotid/transcranial Doppler ultrasonography if computed tomography angiography was contraindicated.Main outcomes and measuresThe primary outcomes were the prevalence and prognosis of asymptomatic ICS.ResultsOf 1368 eligible patients (mean [SD] age, 69.2 [13.9] years; 700 men [51.2%]) with intracranial vascular imaging, 426 ICS were identified in 260 patients (19.0%): 58 (4.2%) with only symptomatic ICS, 155 (11.3%) with only asymptomatic ICS, and 47 (3.4%) with both. The prevalence of any asymptomatic ICS increased from 4.8% for patients younger than 70 years to 34.6% for patients 90 years or older (P for trend < .001; odds ratio per decade, 1.96; 95% CI, 1.69-2.27) and was greater than that of 50% or more asymptomatic carotid bifurcation stenosis (202 [14.8%] vs 105 patients [7.2%]; relative risk, 2.04; 95% CI, 1.63-2.55, P < .001). However, the 155 patients with only asymptomatic ICS had no increase in risk of ischemic stroke compared with those with no ICS (unadjusted HR, 1.03, 95% CI, 0.49-2.17), with 8 first recurrent events (5.2%) during 506 patient-years of follow-up and 3 in the territory of the ICS (annualized risk, 0.59%; 95% CI, 0.12-1.73).Conclusions and relevanceThe prevalence of asymptomatic ICS increases with age in white patients with TIA and minor stroke and is greater than that of asymptomatic carotid stenosis, but asymptomatic ICS does not increase the short- or medium-term risk of distal recurrent ischemic stroke for patients receiving standard medical treatment.
| S-EPMC7251503 | biostudies-literature
Project description:Circulating microRNAs have been shown to be biomarkers of various diseases. We aimed to investigate whether circulating microRNA can serve as a biomarker to predict ischemic stroke risk in asymptomatic intracranial artery stenosis. A total of 716 participants from the Asymptomatic Polyvascular Abnormalities Community study who had asymptomatic intracranial artery stenosis at baseline were enrolled (2010-11). Patients who suffered incident ischemic stroke were classified into the case group, and age- and sex-matched individuals without stroke were used as controls. MicroRNA microarrays were used to distinguish baseline circulating serum microRNA levels between the case and the control groups (GEO accession number GSE201860). The differentially expressed microRNAs were validated by real-time PCR. MicroRNA microarrays were performed in baseline serum samples from12 subjects who developed ischemic stroke and 12 age- and sex-matched subjects without stroke during the 2014-15 follow-up period. Twenty microRNAs were differentially expressed between the two groups (fold change > 1.3 and p < 0.05 for all). Hsa-miR-486-5p, hsa-miR-92a-3p, hsa-miR-6089 from them were selected and validated in the baseline serum samples of ten subjects with incident ischemic stroke and another ten age- and sex-matched subjects without stroke during the 2016-17 follow-up period. Hsa-miR-1225-5p, with a large fold change value and a reported relationship with cardiovascular or cerebrovascular diseases, was also validated. Ultimately, only hsa-miR-6089 was differentially downregulated among patients with intracranial artery stenosis who developed ischemic stroke (p < 0.05). In patients with asymptomatic intracranial artery stenosis, downregulated serum hsa-miR-6089 may be associated with the risk of ischemic stroke.
| S-EPMC11412422 | biostudies-literature
Project description:ObjectiveAcute ischemic stroke (AIS) is characterized by high rates of morbidity, disability, mortality, and recurrence, often leaving patients with varying degrees of sequelae. Symptomatic intracranial atherosclerotic stenosis (sICAS) is a significant contributor to AIS pathogenesis and recurrence. The formation and progression of sICAS are influenced by pathways such as lipid metabolism and inflammatory response. Given its high risk of clinical recurrence, timely assessment of intracranial vascular stenosis in AIS is crucial for diagnosing sICAS, treating stroke, and preventing stroke recurrence.MethodsFourteen AIS patients were divided into stenosis and control groups based on the presence or absence of intracranial vessel stenosis. Initially, 4D Label-free proteome quantification technology was employed for mass spectrometry analysis to identify differential proteins between the groups. Subsequently, functional enrichment analysis, including GO classification, KEGG pathway, and Domain, revealed trends related to differential proteins. The STRING (v.11.5) protein interaction network database was used to identify differential protein interactions and target proteins. Finally, parallel reaction monitoring (PRM) validated the selected target proteins.ResultsMass spectrometry identified 1,096 proteins, with 991 being quantitatively comparable. Using a p-value <0.05 and differential expression change thresholds of >1.3 for significant up-regulation and < 1/1.3 for significant down-regulation, 46 differential proteins were identified: 24 significantly up-regulated and 22 significantly down-regulated. PRM experiments validated five proteins related to lipid metabolism and inflammatory response: namely alpha-2-macroglobulin (A2M), lipopolysaccharide-binding protein (LBP), cathepsin G (CTSG), cystatin (CST)3, and fatty acid-binding protein (FABP)1.ConclusionThe detection of changes in these five proteins in AIS patients can aid in the diagnosis of sICAS, inform stroke treatment, and assist in preventing stroke recurrence. Moreover, it can contribute to the development of drugs for preventing AIS recurrence by integrating traditional Chinese and Western medicine.
| S-EPMC10711507 | biostudies-literature
Project description:ImportanceOptimal management of patients with asymptomatic severe carotid stenosis is uncertain, due to advances in medical care and a lack of contemporary data comparing medical and surgical treatment.ObjectiveTo estimate stroke outcomes among patients with medically treated asymptomatic severe carotid stenosis who did not undergo surgical intervention.Design, setting, and participantsRetrospective cohort study that included 3737 adult participants with asymptomatic severe (70%-99%) carotid stenosis diagnosed between 2008 and 2012 and no prior intervention or ipsilateral neurologic event in the prior 6 months. Participants received follow-up through 2019, and all were members of an integrated US regional health system serving 4.5 million members.ExposuresImaging diagnosis of asymptomatic carotid stenosis of 70% to 99%.Main outcomes and measuresOccurrence of ipsilateral carotid-related acute ischemic stroke. Censoring occurred with death, disenrollment, or ipsilateral intervention.ResultsAmong 94 822 patients with qualifying imaging studies, 4230 arteries in 3737 (mean age, 73.8 [SD 9.5 years]; 57.4% male) patients met selection criteria including 2539 arteries in 2314 patients who never received intervention. The mean follow-up in this cohort was 4.1 years (SD 3.6 years). Prior to any intervention, there were 133 ipsilateral strokes with a mean annual stroke rate of 0.9% (95% confidence interval [CI], 0.7%-1.2%). The Kaplan-Meier estimate of ipsilateral stroke by 5 years was 4.7% (95% CI, 3.9%-5.7%).Conclusions and relevanceIn a community-based cohort of patients with asymptomatic severe carotid stenosis who did not undergo surgical intervention, the estimated rate of ipsilateral carotid-related acute ischemic stroke was 4.7% over 5 years. These findings may inform decision-making regarding surgical and medical treatment for patients with asymptomatic severe carotid artery stenosis.
| S-EPMC9131743 | biostudies-literature
Project description:Gene expression information is useful in prioritizing candidate genes in linkage intervals. The data can also identify pathways involved in the pathophysiology of disease. We used microarrays to identify which genes are expressed in either intracranial arteries (control) or in intracranial aneurysms (case), and can therefore contribute to the disease phenotypes. We used microarrays to identify the pathway membership of expressed genes and the overrepresentation of pathways with expressed genes in the known linkage intervals for intracranial aneurysms. Keywords: Characterization of expression in both diseased and non-diseased intracranial arteries.
2007-11-20 | GSE6551 | GEO
Project description:BackgroundThe safety and efficacy of dual antiplatelet therapy (DAPT) in ischemic stroke patients with intracranial artery stenosis (ICAS) remain contentious.AimsThis study evaluates DAPT's effectiveness and safety for these patients.MethodsThis review was reported following PRISMA 2020 guidelines. A comprehensive search was conducted in PubMed, Embase, Cochrane Library, ClinicalTrials.gov, CNKI, WanFang, VIP, and SinoMed up to June 20, 2023, for randomized controlled trials comparing efficacy and safety of DAPT against single antiplatelet therapy (SAPT) in ischemic stroke patients with ICAS. The primary outcome was a composite of ischemic and bleeding events. Secondary outcomes included stroke (cerebral infarction and hemorrhage), ischemic events, and cerebral infarction. Safety outcomes assessed were bleeding events, cerebral hemorrhage, and mortality. Risk ratios (RRs) with 95% confidence intervals (CIs) were synthesized using Review Manager 5.4.ResultsAnalysis of 21 randomized controlled trials involving 3,591 patients revealed that DAPT significantly lowered the rate of ischemic and bleeding events (RR = 0.52; 95% CI: 0.46-0.59, p < 0.001) and recurrent stroke (RR = 0.37; 95% CI: 0.30-0.44, p < 0.001) compared to SAPT. There was no significant increase in bleeding events (RR = 1.34; 95% CI: 0.97-1.85, p = 0.07) or cerebral hemorrhage (RR = 0.47; 95% CI: 0.17-1.31, p = 0.15).ConclusionDAPT proveed to be effective and safe for ischemic stroke patients with ICAS and significantly reduced stroke and the composite endpoint of ischemic and bleeding events without elevating bleeding risks.
| S-EPMC11194412 | biostudies-literature
Project description:To examine molecular mechanisms of aortic valve stenosis in mice with hypertension and hypercholesterolemia, RNA-Seq was used during the developmental phase of stenosis to identify new gene targets.
2016-03-07 | GSE71534 | GEO