Circulating MicroRNAs as Biomarkers of Acute Stroke

Sepramaniam, Sugunavathi; Tan, Jun-Rong; Tan, Kay Sin; Silva, Deidre Anne De; Tavintharan, Subramaniam; Woon, Fung‐Peng; Wang, Chee-Woon; Yong, Fung-Lin; Karolina, Dwi-Setyowati; Kaur, Prameet; Liu, Fujia; Lim, Kai-Ying; Armugam, Arunmozhiarasi; Jeyaseelan, Kandiah

doi:10.3390/ijms15011418

Cited by 158 publications

(125 citation statements)

References 30 publications

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“…Hundreds of genes may have an impact on stroke pathogenesis or are associated with risk factors [8]. However, their specificity and ability to distinguish among different phases of stroke, especially the hyperacute phase, or symptoms resembling stroke is uncertain [9]. Therefore, we attempted to seek a biomarker for the diagnosis of hyperacute IS, analogous to troponin in the assessment of myocardial infarction.…”

Section: Introductionmentioning

confidence: 99%

Diagnosis of Hyperacute and Acute Ischaemic Stroke: The Potential Utility of Exosomal MicroRNA-21-5p and MicroRNA-30a-5p

Wang

et al. 2018

Cerebrovasc Dis

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Background: Early and accurate diagnosis of ischaemic stroke (IS) requires the use of an optimized biomarker. Exosomal microRNAs have the potential to serve as biomarkers owing to their stability and specificity. We investigated the expression levels of plasma-derived exosomal microRNA-21-5p and microRNA-30a-5p in the different phases of IS. Methods: One hundred forty-three patients with IS and 24 non-stroke controls were enrolled. The patients were divided into the following 5 groups: 1 group for the hyperacute phase IS (HIS, within 6 h); two for the acute phase IS (AIS, including days 1–3 and days 4–7); one for the subacute phase IS (SIS, days 8–14); and one for the recovery phase IS (RIS, days >14). Plasma exosomes were isolated using a QIAGEN exoRNeasy kit and examined by transmission electron microscopy, nanoparticle tracking, and flow cytometry. The expression levels of miRNA-21-5p and miRNA-30a-5p were detected by quantitative real-time polymerase chain reaction. Results: The plasma exosomal miR-21-5p levels in SIS and RIS were significantly higher than that in controls (p < 0.05 and p < 0.01 respectively). The levels of miR-30a-5p in HIS were significantly higher (p < 0.05) and in AIS (days 1–3) were lower than that in controls (p < 0.05). In AIS (days 1–3), both miRNAs were decreased compared with the HIS group (p = 0.053 and 0.001, respectively). The area under the curve (AUC) of the miR-21-5p was 0.714 for SIS (95% CI 0.570–0.859, p = 0.007), 0.734 for RIS (95% CI 0.596–0.871, p = 0.003); the AUC of the miR-30a-5p was 0.826 for HIS (95% CI 0.665–0.988, p = 0.001), 0.438 for AIS (days 1–3; 95% CI 0.240–0.635, p = 0.516). Conclusions: The plasma-derived exosomal miR-21-5p and miRNA-30a-5p in combination are promising biomarkers for diagnosing IS and distinguishing among HIS, SIS, and RIS, especially miRNA-30a-5p for the diagnosis of the HIS phase. Our results provide a new reference for clinicians to apply in early-stage diagnosis and identifies the possible value of biomarkers for IS thrombolysis therapy.

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Section: Introductionmentioning

confidence: 99%

Diagnosis of Hyperacute and Acute Ischaemic Stroke: The Potential Utility of Exosomal MicroRNA-21-5p and MicroRNA-30a-5p

Wang

et al. 2018

Cerebrovasc Dis

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“…Upregulation of miR-125b-2*, miR-27a*, miR-422a, miR-488 and miR-627 were consistently observed in patients with acute stroke, irrespective of age, severity, or confounding metabolic complications. The same five miRNAs were also upregulated in a rat model of middle cerebral artery occlusion, further supporting that the change in expression was as a result of acute cerebral ischemia [38].…”

Section: Mirna In Cerebrovascular Diseasesmentioning

confidence: 57%

“…Ischemic brain injury has been shown to change expressions of miRNA in animal models of cerebral ischemia and in stroke patients, suggesting that miRNAs are involved in the early stress response to ischemic insult to the brain [36,37]. Sepramaniam et al demonstrated that stroke patients have specific miRNAs expression that can distinguish stroke subtypes [38]. Upregulation of miR-125b-2*, miR-27a*, miR-422a, miR-488 and miR-627 were consistently observed in patients with acute stroke, irrespective of age, severity, or confounding metabolic complications.…”

Section: Mirna In Cerebrovascular Diseasesmentioning

confidence: 99%

MicroRNAs as Potential Prognosticators of Neurological Outcome in Out-Of-Hospital Cardiac Arrest Patients

et al. 2017

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Out-of-hospital cardiac arrest survival rates have increased due to advancement in resuscitative measures, yet approximately 90% of survivors ultimately die or have severe neurologic dysfunction caused by ischemic injury. Currently, there are few early prognostic indicators of which patients have possibility of meaningful recovery. This leads to uncertainty for families and clinicians, as well as aggressive, invasive and expensive treatments despite medical futility. Several biomarkers investigated in traumatic brain injury have shown prognostication potential in ischemic brain injury. miRNAs, small noncoding RNAs responsible for gene regulation, have been studied in cardiovascular diseases, and have shown prognostication potential due to tissue specificity and stability in circulation. This review discusses available evidence on miRNAs prognosticating neurological outcomes after out-of-hospital cardiac arrest.

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“…Since many [71]. In stroke field, increased or decreased levels of several circulating microRNA were reported in isch emic stroke patients [72,73]. For example, microRNA424 lev el was decreased in acute stroke patients and in an animal model of stroke, and intracerebroventricular injection of len tiviral microRNA424 reduced ischemic brain injury [72].…”

Section: Micrornasmentioning

confidence: 99%

Advances in biomarker for stroke patients: from marker to regulator

Bang

2017

Precis Future Med

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Biomarkers refer to indicators found in the blood, other body fluids or tissues that pre dict physiologic or disease states, increased disease risk, or pharmacologic responses to a therapeutic intervention. Stroke is a heterogeneous condition, and stroke biomark ers could be used as a guiding tool for more effective personalized therapy. In this review, the recent advances in the biomarkers in stroke field are discussed. First, various types of biomarkers including genetic, extracellular vesicle, and metabolomicsassociated biomarkers as well as protein biomarkers were recently introduced. The studies reviewed herein suggest that comprehensive analysis of different types of stroke biomarkers will improve the understanding of individual pathophysiologies and further promote the development of screening tool of highrisk patients, predicting model of stroke outcome and rational stroke therapy tailored to the characteristics of each case. Second, several biomarkers can be bio'makers' that regulate compensatory or pathological process in the development of stroke etiology and recovery after stroke. Several protein (e.g., chemokines, caveoli), genetic (e.g., microRNA), and extracellular vesicles (e.g., cancer cell, stem cellsderived) may be directly involved in these processes. These biomakers may be molecular target of treatment and can be used for new drug development.

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Circulating MicroRNAs as Biomarkers of Acute Stroke

Cited by 158 publications

References 30 publications

Diagnosis of Hyperacute and Acute Ischaemic Stroke: The Potential Utility of Exosomal MicroRNA-21-5p and MicroRNA-30a-5p

Diagnosis of Hyperacute and Acute Ischaemic Stroke: The Potential Utility of Exosomal MicroRNA-21-5p and MicroRNA-30a-5p

MicroRNAs as Potential Prognosticators of Neurological Outcome in Out-Of-Hospital Cardiac Arrest Patients

Advances in biomarker for stroke patients: from marker to regulator

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