Increased expression of <scp>STIM</scp>1/Orai1 in platelets of stroke patients predictive of poor outcomes

Dong, Ming; Zheng, Na; Ren, Lijie; Zhou, Hongjian; Liu, J.

doi:10.1111/ene.13304

Cited by 10 publications

(8 citation statements)

References 24 publications

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“…This was first described in the setting of (experimental) stroke, where platelets and T cells drive secondary thrombo-inflammatory brain infarct growth despite successful recanalization of the previously occluded brain artery. Recent experimental data has highlighted a critical role of the platelet GPVI/LAT/PLCγ2/STIM1/Orai1 axis in this process (9, 10, 43), and increased expression levels of STIM1/Orai1 have been proposed to serve as a predictor for poor outcome of stroke (44). To assess the pathophysiological significance of BIN2-dependent SOCE in this process, we subjected Bin2 fl/fl,Pf4-Cre mice to the transient middle cerebral artery occlusion (tMCAO) model of ischemic stroke, in which the middle cerebral artery (MCA) was transiently occluded by insertion of a filament as described previously (45).…”

Section: Stim1 Interacts With Bin2 In Plateletsmentioning

confidence: 99%

BIN2 orchestrates platelet calcium signaling in thrombosis and thrombo-inflammation

Volz¹,

Kusch²,

Beck³

et al. 2020

Journal of Clinical Investigation

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Section: Stim1 Interacts With Bin2 In Plateletsmentioning

confidence: 99%

BIN2 orchestrates platelet calcium signaling in thrombosis and thrombo-inflammation

Volz¹,

Kusch²,

Beck³

et al. 2020

Journal of Clinical Investigation

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“…This process offers protectionto mice from ischemic stroke [61]. Dong M et al reported that STIM1/Orai1 expression was associated with mortality and recurrence in ischemic stroke patients and was an independent predictor of the 3-month stroke recovery [62].…”

Section: Discussionmentioning

confidence: 99%

Hub Genes of Stroke Identified by Weighted Gene Co-expression Network Analysis

Zhai

et al. 2020

Preprint

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BACKGROUD: Microarray-based gene expression profiling is widely used in biomedical research. Weighted gene co-expression network analysis (WGCNA) links microarray data directly to clinical traits and identifies rules for predicting pathological stage and prognosis of disease.WGCNA is useful in understandingmany biological processes. Stroke is a common disease worldwide, however, molecular mechanisms of its pathogenesis are largely unknown. The aim of this study was to construct gene co-expression networks for identification of key modules and hub genes associated with stroke pathogenesis.METHODS: Gene microarray expression profiles of stroke samples were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened by the limma package in R software. WGCNA was used to construct free-scale gene co-expression networks to explore the associations between gene sets and clinical features, and to identify key modules and hub genes. Subsequently, functional enrichment analyses were performed. Further, receiver operating characteristic (ROC) curve analysis was carried out to validate expression of hub genes and literature validation was performed as well.RESULTS: A total of 11,747 most variant genes were used for co-expression network construction. Pink and yellow modules were significantly correlated to stroke pathogenesis. Functional enrichment analysis showed that the pink module was mainly involved in regulation of neuron regeneration, and repair of DNA damage.On the other hand, yellow module was mainly enriched in ion transport system dysfunction which was correlated with neuron death. A total of eight hub genes (PRR11, NEDD9, Notch2, RUNX1-IT1, ANP32A-IT1, ASTN2, SAMHD1 and STIM1) were identified and validated at transcriptional levels and through existing literature.CONCLUSION: The eight hub genes (PRR11, NEDD9, Notch2, RUNX1-IT1, ANP32A-IT1, ASTN2, SAMHD1 and STIM1) identified in the study are potentialbiomarkers and therapeutic targets for effective diagnosis and treatment of stroke.

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“…Several potential mechanisms consist of endothelial dysfunction, [24] oxidative stress, [25] activation of inflammation, [26] proliferation of smooth-muscle, increased adhesion of monocytes to endothelial cells [27] and platelet dysfunction. [28,29]…”

Section: Discussionmentioning

confidence: 99%

Relationship between serum homocysteine levels and long-term outcomes in patients with ST-segment elevation myocardial infarction

Jin

Wang

et al. 2019

Chinese Medical Journal

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Background: The mortality of cardiovascular disease is constantly rising, and novel biomarkers help us predict residual risk. This study aimed to evaluate the predictive value of serum homocysteine (HCY) levels on prognosis in patients with ST-segment elevation myocardial infarction (STEMI). Methods: The 419 consecutive patients with STEMI, treated at one medical center, from March 2010 to December 2015 were retrospectively investigated. Peripheral blood samples were obtained within 24 h of admission and HCY concentrations were measured using an enzymatic cycling assay. The patients were divided into high HCY level (H-HCY) and low HCY level (L-HCY) groups. Short- and long-term outcomes were compared, as were age-based subgroups (patients aged 60 years and younger vs . those older than 60 years). Statistical analyses were mainly conducted by Student t -test, Chi-squared test, logistic regression, and Cox proportional-hazards regression. Results: The H-HCY group had more males (84.6% vs . 75.4%, P = 0.018), and a lower prevalence of diabetes (20.2% vs . 35.5%, P < 0.001), compared with the L-HCY group. During hospitalization, there were seven mortalities in the L-HCY group and 10 in the H-HCY group (3.3% vs . 4.8%, P = 0.440). During the median follow-up period of 35.8 (26.9–46.1) months, 33 (16.2%) patients in the L-HCY group and 48 (24.2%) in the H-HCY group experienced major adverse cardiovascular and cerebrovascular events (MACCE) ( P = 0.120). History of hypertension (hazard ratio [HR]: 1.881, 95% confidence interval [CI]: 1.178–3.005, P = 0.008) and higher Killip class (HR: 1.923, 95% CI: 1.419–2.607, P < 0.001), but not HCY levels (HR: 1.007, 95% CI: 0.987–1.027, P = 0.507), were significantly associated with long-term outcomes. However, the subgroup analysis indicated that in older patients, HCY levels were significantly associated with long-term outcomes (HR: 1.036, 95% CI: 1.011–1.062, P = 0.005). Conclusion: Serum HCY levels did not independently predict in-hospital or long-term outcomes in patients with STEMI; however, among elderly patients with STEMI, this study revealed a risk profile for late outcomes that incorporated HCY level.

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Increased expression of STIM1/Orai1 in platelets of stroke patients predictive of poor outcomes

Abstract: A high expression level of platelet Orai1/STIMI1 was associated with poor clinical outcome (mortality and recurrence) and functional recovery (SIS scores) during the 3-month follow-up. Thus, we propose that these proteins are strongly predictive of life quality in patients with IS.

Cited by 10 publications

References 24 publications

BIN2 orchestrates platelet calcium signaling in thrombosis and thrombo-inflammation

BIN2 orchestrates platelet calcium signaling in thrombosis and thrombo-inflammation

Hub Genes of Stroke Identified by Weighted Gene Co-expression Network Analysis

Relationship between serum homocysteine levels and long-term outcomes in patients with ST-segment elevation myocardial infarction

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