Dataset Information

Gene expression differences between stroke-associated and asymptomatic carotid plaques.

ABSTRACT: Atherosclerotic carotid stenosis is an important risk factor for stroke. Carotid plaques (CPs) causing stroke may present a distinct type of molecular pathology compared with transient ischemic attack (TIA)-associated or asymptomatic plaques. We compared the gene expression profiles of CPs from stroke patients (n?=?12) and asymptomatic patients (n?=?9), both with similar risk factors and severity of carotid stenosis (>70%). Sixty probes showed over 1.5-fold expression difference at 5% false discovery rate. Functional clustering showed enrichment of genes in 51 GO categories and seven pathways, the most significant of which relate to extracellular-matrix interaction, PPAR gamma signaling, scavanger receptor activity, and lysosomal activity. Differential expression of ten genes was confirmed in an extended replication group (n?=?43), where the most significant expression differences were found in CD36 (2.1-fold change, p?=?0.005), CD163 (1.7-fold change, p?=?0.007) and FABP4 (2.2-fold change, p?=?0.015). These include four genes not previously linked to plaque destabilization: GLUL (2.2-fold change, p?=?0.016), FUCA1 (2.2-fold change, p?=?0.025), IL1RN (1.6-fold change, p?=?0.034), and S100A8 (2.5-fold change, p?=?0.047). Strong correlations were found to plaque ulceration, plaque hemorrhage, and markers of apoptosis and proliferation (activated caspase 3, TUNEL, and Ki67). Protein expression of these genes was confirmed by immunohistochemistry and was found in the atheromatous areas of CPs critical for plaque destabilization. This study presents a comprehensive transcriptional analysis of stroke-associated CPs and demonstrates a significant transcriptome difference between stroke-associated and asymptomatic CPs. Follow-up studies on the identified genes are needed to define whether they could be used as biomarkers of symptomatic CPs or have a role in plaque destabilization.

SUBMITTER: Saksi J

PROVIDER: S-EPMC3170468 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Gene expression differences between stroke-associated and asymptomatic carotid plaques.

Saksi Jani J Ijäs Petra P Nuotio Krista K Sonninen Riitta R Soinne Lauri L Salonen Oili O Saimanen Eija E Tuimala Jarno J Lehtonen-Smeds Erno M EM Kaste Markku M Kovanen Petri T PT Lindsberg Perttu J PJ

Journal of molecular medicine (Berlin, Germany) 20110524 10

Atherosclerotic carotid stenosis is an important risk factor for stroke. Carotid plaques (CPs) causing stroke may present a distinct type of molecular pathology compared with transient ischemic attack (TIA)-associated or asymptomatic plaques. We compared the gene expression profiles of CPs from stroke patients (n = 12) and asymptomatic patients (n = 9), both with similar risk factors and severity of carotid stenosis (>70%). Sixty probes showed over 1.5-fold expression difference at 5% false disc ...[more]

PMID: 21607540

Similar Datasets

Project description:ImportanceThere is an ongoing debate regarding the management of asymptomatic carotid stenosis. Previous studies have reported imaging features of high-risk plaques that could help to optimize the risk-benefit ratio of revascularization. However, such studies have not provided an accurate estimate of the prevalence of high-risk plaques and the associated annual incidence of ipsilateral ischemic cerebrovascular events to inform the design of clinical trials using a risk-oriented selection of patients before randomization.ObjectiveTo assess the relevance and feasibility of risk-oriented selection of patients for revascularization.Data sourcesA systematic search of PubMed and Ovid Embase from database inception to July 31, 2019, was performed.Study selectionProspective observational studies that reported prevalence of high-risk plaques and incidence of ipsilateral ischemic cerebrovascular events were included.Data extraction and synthesisAggregated data were pooled using random-effects meta-analysis. Data were analyzed from December 16, 2019, to January 15, 2020.Main outcomes and measuresPrevalence of high-risk plaques and annual incidence of ipsilateral ischemic events.ResultsOverall, 64 studies enrolling 20 751 participants aged 29 to 95 years (mean age range, 55.0-76.5 years; proportion of men, 45%-87%) were included in the meta-analysis. Among all participants, the pooled prevalence of high-risk plaques was 26.5% (95% CI, 22.9%-30.3%). The most prevalent high-risk plaque features were neovascularization (43.4%; 95% CI, 31.4%-55.8%) in 785 participants, echolucency (42.3%; 95% CI, 32.2%-52.8%) in 12 364 participants, and lipid-rich necrotic core (36.3%; 95% CI, 27.7%-45.2%) in 3728 participants. The overall incidence of ipsilateral ischemic cerebrovascular events was 3.2 events per 100 person-years (22 cohorts with 10 381 participants; mean follow-up period, 2.8 years; range, 0.7-6.5 years). The incidence of ipsilateral ischemic cerebrovascular events was higher in patients with high-risk plaques (4.3 events per 100 person-years; 95% CI, 2.5-6.5 events per 100 person-years) than in those without high-risk plaques (1.2 events per 100 person-years; 95% CI, 0.6-1.8 events per 100 person-years), with an odds ratio of 3.0 (95% CI, 2.1-4.3; I2 = 48.8%). In studies focusing on severe stenosis (9 cohorts with 2128 participants; mean follow-up period, 2.8 years; range, 1.4-6.5 years), the incidence of ipsilateral ischemic cerebrovascular events was 3.7 events per 100 person-years (95% CI, 1.9-6.0 events per 100 person-years). The incidence of ipsilateral ischemic cerebrovascular events was also higher in patients with high-risk plaques (7.3 events per 100 person-years; 95% CI, 2.0-15.0 events per 100 person-years) than in those without high-risk plaques (1.7 events per 100 person-years; 95% CI, 0.6-3.3 events per 100 person-years), with an odds ratio of 3.2 (95% CI, 1.7-5.9; I2 = 39.6%).Conclusions and relevanceHigh-risk plaques are common in patients with asymptomatic carotid stenosis, and the associated risk of an ipsilateral ischemic cerebrovascular event is higher than the currently accepted estimates. Extension of routine assessment of asymptomatic carotid stenosis beyond the grade of stenosis may help improve risk stratification and optimize therapy.

Dataset Information

Gene expression differences between stroke-associated and asymptomatic carotid plaques.

Publications

Gene expression differences between stroke-associated and asymptomatic carotid plaques.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets