Dataset Information

Proinflammatory protein signatures in cryptogenic and large artery atherosclerosis stroke.

ABSTRACT:

Objectives

The cause of ischemic stroke remains unknown, cryptogenic, in 25% of young and middle-aged patients. We hypothesized that if atherosclerosis is prominent in cryptogenic stroke, it would have a similar proinflammatory protein signature as large artery atherosclerosis (LAA) stroke.

Materials & methods

Blood was collected in the acute phase and after 3 months from cryptogenic (n = 162) and LAA (n = 73) stroke patients aged 18-69 years and once from age-matched controls (n = 235). Cryptogenic stroke was divided into Framingham Risk Score (FRS) quartiles to compare low and high risk of atherosclerosis. Plasma concentrations of 25 proteins were analyzed using a Luminex multiplex assay. The discriminating properties were assessed with discriminant analysis and C-statistics.

Results

We identified proteins that separated cryptogenic and LAA stroke from controls (area under the curves, AUCs ? 0.85). For both subtypes, RANTES, IL-4, and IFN-? contributed the most at both time points. These associations were independent of risk factors of atherosclerosis. We also identified proteins that separated cryptogenic strokes in the lowest quartile of FRS from those in the highest, and from LAA stroke (AUCs ? 0.76), and here eotaxin and MCP-1 contributed the most.

Conclusions

The protein signature separating cases from controls was different from the signature separating cryptogenic stroke with low risk of atherosclerosis from those with high risk and from LAA stroke. This suggests that increased RANTES, IL-4, and IFN-? in stroke may not be primarily related to atherosclerosis, whereas increased eotaxin and MCP-1 in cryptogenic stroke may be markers of occult atherosclerosis as the underlying cause.

SUBMITTER: Holmegaard L

PROVIDER: S-EPMC7898473 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Proinflammatory protein signatures in cryptogenic and large artery atherosclerosis stroke.

Holmegaard Lukas L Stanne Tara M TM Andreasson Ulf U Zetterberg Henrik H Blennow Kaj K Blomstrand Christian C Jood Katarina K Jern Christina C

Acta neurologica Scandinavica 20201204 3

<h4>Objectives</h4>The cause of ischemic stroke remains unknown, cryptogenic, in 25% of young and middle-aged patients. We hypothesized that if atherosclerosis is prominent in cryptogenic stroke, it would have a similar proinflammatory protein signature as large artery atherosclerosis (LAA) stroke.<h4>Materials & methods</h4>Blood was collected in the acute phase and after 3 months from cryptogenic (n = 162) and LAA (n = 73) stroke patients aged 18-69 years and once from age-matched controls (n ...[more]

PMID: 33107019

Similar Datasets

Project description:Purpose: This study aimed to explore the differential expression profiles of exosomal lncRNAs and evaluated their potential utility in the accurate diagnosis of LAA stroke. Methods: LncRNA profiles of exosomes in large artery atherosclerosis stroke and controls were generated by high-throughput sequencing. The sequence reads that passed quality filters were analyzed at the transcript isoform level with Hisat2, Trapnell, STAR. qRT–PCR validation was performed using TaqMan and SYBR Green assays. Results: A total of 1020 differentially expressed lncRNAs were identified in LAA stroke patients. GO and KEGG pathway analyses indicated that their target genes are involved in atherosclerosis-related pathways, including inflammation, cell adhesion, and cell migration. 8 exosomal lncRNAs were confirmed with qRT–PCR.The result showed that the expression trend of differential expressed lncRNAs in validation was consistent with RNA-seq.Conclusion: Our study showed the differential expression of lncRNAs in plasma exosomes and presented related diagnostic potential for LAA stroke for the first time. The results suggested that exosomal lncRNA could be potential diagnostic tools in LAA stroke. Circular RNAs (circRNAs), novel endogenous noncoding RNAs, play diverse roles in ischemic stroke. Recently, the abundance and stability of circRNAs in exosomes have been identified. However, a comprehensive analysis of exosomal circRNAs in large artery atherosclerotic (LAA) stroke has not yet been reported. We performed RNA sequencing (RNA-Seq) to comprehensively identify differentially expressed exosomal circRNAs in five paired LAA and normal controls. RNA-Seq identified a total of 462 circRNAs in peripheral exosomes; there were 25 differentially expressed circRNAs among them. Additionally, circRNA competing endogenous RNA (ceRNA) network and translatable analysis revealed the potential functions of the exosomal circRNAs in LAA progression. Two ceRNA pathways involving 5 circRNAs, 2 miRNAs, and 3 mRNAs were confirmed by qRT-PCR. In the validation cohort, receiver operating characteristic (ROC) curve analysis identified two circRNAs as possible novel biomarkers, and a logistic model combining two and four circRNAs increased the area under the curve compared with the individual circRNAs.

Project description:IntroductionStroke etiology may affect the prognosis of acute basilar artery occlusion (BAO). This study aimed to estimate the efficacy and safety of endovascular treatment (EVT) in BAO strokes due to the underlying stroke etiologies of large artery atherosclerosis (LAA) and cardioembolism (CE).Patients and methodsPatients with LAA and CE subtypes from the registry EVT for Acute Basilar Artery Occlusion Study (BASILAR) were selected for this analysis. We estimated the EVT treatment effect relative to standard medical treatment (SMT) in these patients by using a propensity score approach with inverse probability of treatment weighted estimation. Outcomes included 90-day favorable functional outcomes (modified Rankin scale (mRS) 0-3), functional independence (mRS 0-2), all-cause mortality, and symptomatic intracranial hemorrhage (sICH).ResultsA total of 744 patients were included in the final analysis. After weighting with inverse probability of treatment estimation, the patients who, based on their characteristics, were treated with EVT rather than SMT, demonstrated higher rates of favorable functional outcomes in both the LAA (29.2% vs 11.7%, adjusted OR with 95% CI: 4.34 [2.15-8.78], p < 0.001) and the CE subtype (36.0% vs 8.1%, adjusted OR with 95% CI: 9.14 [1.96-42.55], p = 0.005). A similar finding was also observed for functional independence. EVT patients also demonstrated lower rates of mortality than SMT. Among EVT patients, no significant difference was observed in mortality or sICH between LAA and CE groups, but LAA patients had lower rates of favorable functional outcome and functional independence (29.2% vs 37% and 24.2% vs 32.9%, respectively), where the latter remained significant after adjustment for imbalances in baseline data (p = 0.04).ConclusionsIn acute BAO strokes, both LAA and CE patients who, based on their characteristics, were treated with EVT rather than SMT, demonstrated better outcomes. Among EVT patients, LAA and CE subtypes displayed important baseline and treatment differences, and LAA patients were less likely to achieve functional independence at 3 months, but mortality and sICH were similar between LAA or CE subtypes. These results need to be confirmed in future clinical trials.

Dataset Information

Proinflammatory protein signatures in cryptogenic and large artery atherosclerosis stroke.

Objectives

Materials & methods

Results

Conclusions

Publications

Proinflammatory protein signatures in cryptogenic and large artery atherosclerosis stroke.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets