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Diagnostic Performance of Circulating miRNAs and Extracellular Vesicles in Acute Ischemic Stroke. / Eyileten, Ceren; Jakubik, Daniel; Shahzadi, Andleeb et al.

In: International journal of molecular sciences, Vol. 23, No. 9, 4530, 01.05.2022.

Research output: Contribution to journalArticleAcademicpeer-review

Harvard

Eyileten, C, Jakubik, D, Shahzadi, A, Gasecka, A, van der Pol, E, de Rosa, S, Siwik, D, Gajewska, M, Mirowska-Guzel, D, Kurkowska-Jastrzebska, I, Czlonkowska, A & Postula, M 2022, 'Diagnostic Performance of Circulating miRNAs and Extracellular Vesicles in Acute Ischemic Stroke', International journal of molecular sciences, vol. 23, no. 9, 4530. https://doi.org/10.3390/ijms23094530

APA

Eyileten, C., Jakubik, D., Shahzadi, A., Gasecka, A., van der Pol, E., de Rosa, S., Siwik, D., Gajewska, M., Mirowska-Guzel, D., Kurkowska-Jastrzebska, I., Czlonkowska, A., & Postula, M. (2022). Diagnostic Performance of Circulating miRNAs and Extracellular Vesicles in Acute Ischemic Stroke. International journal of molecular sciences, 23(9), [4530]. https://doi.org/10.3390/ijms23094530

Vancouver

Eyileten C, Jakubik D, Shahzadi A, Gasecka A, van der Pol E, de Rosa S et al. Diagnostic Performance of Circulating miRNAs and Extracellular Vesicles in Acute Ischemic Stroke. International journal of molecular sciences. 2022 May 1;23(9). 4530. https://doi.org/10.3390/ijms23094530

Author

Eyileten, Ceren ; Jakubik, Daniel ; Shahzadi, Andleeb et al. / Diagnostic Performance of Circulating miRNAs and Extracellular Vesicles in Acute Ischemic Stroke. In: International journal of molecular sciences. 2022 ; Vol. 23, No. 9.

BibTeX

@article{b3903325acd34bd0b5c2766270b2a5ca,
title = "Diagnostic Performance of Circulating miRNAs and Extracellular Vesicles in Acute Ischemic Stroke",
abstract = "Background: Increased inflammation activates blood coagulation system, higher platelet activation plays a key role in the pathophysiology of ischemic stroke (IS). During platelet activation and aggregation process, platelets may cause increased release of several proinflammatory, and prothrombotic mediators, including microRNAs (miRNAs) and extracellular vesicles (EVs). In the current study we aimed to assess circulating miRNAs profile related to platelet function and inflammation and circulating EVs from platelets, leukocytes, and endothelial cells to analyse their diagnostic and predictive utility in patients with acute IS. Methods: The study population consisted of 28 patients with the diagnosis of the acute IS. The control group consisted of 35 age-and gender-matched patients on acetylsalicylic acid (ASA) therapy without history of stroke and/or TIA with established stable coronary artery disease (CAD) and concomitant cardiovascular risk factors. Venous blood samples were collected from the control group and patients with IS on ASA therapy (a) 24 h after onset of acute IS, (b) 7-days following index hospitalization. Flow cytometry was used to determine the concentration of circulating EVs subtypes (from platelets, leukocytes, and endothelial cells) in platelet-depleted plasma and qRT-PCR was used to determine several circulating plasma miRNAs (miR-19a-3p, miR-186-5p and let-7f). Results: Patients with high platelet reactivity (HPR, based on arachidonic acid-induced platelet aggregometry) had significantly elevated platelet-EVs (CD62+) and leukocyte-EVs (CD45+) concentration compared to patients with normal platelet reactivity at the day of 1 acute-stroke (p = 0.012, p = 0.002, respectively). Diagnostic values of baseline miRNAs and EVs were evaluated with receiver operating characteristic (ROC) curve analysis. The area under the ROC curve for miR-19a-3p was 0.755 (95% CI, 0.63–0.88) p = 0.004, for let-7f, it was 0.874 (95% CI, 0.76–0.99) p = 0.0001; platelet-EVs was 0.776 (95% CI, 0.65–0.90) p = 0.001, whereas for leukocyte-EVs, it was 0.715 (95% CI, 0.57–0.87) p = 0.008. ROC curve showed that pooling the miR-19a-3p expressions, platelet-EVs, and leukocyte-EVs concentration yielded a higher AUC than the value of each individual biomarker as AUC was 0.893 (95% CI, 0.79–0.99). Patients with moderate stroke had significantly elevated miR-19a-3p expression levels compared to patients with minor stroke at the first day of IS. (AUC: 0.867, (95% CI, 0.74–0.10) p = 0.001). Conclusion: Combining different biomarkers of processes underlying IS pathophysiology might be beneficial for early diagnosis of ischemic events. Thus, we believe that in the future circulating biomarkers might be used in the prehospital phase of IS. In particular, circulating plasma EVs and non-coding RNAs including miRNAs are interesting candidates as bearers of circulating biomarkers due to their high stability in the blood and making them highly relevant biomarkers for IS diagnostics.",
keywords = "EVs, ischemia, let-7f, leukocyte extracellular vesicles, miR-186, miR-19a, platelet extracellular vesicles, platelet reactivity, prognosis, stroke severity",
author = "Ceren Eyileten and Daniel Jakubik and Andleeb Shahzadi and Aleksandra Gasecka and {van der Pol}, Edwin and {de Rosa}, Salvatore and Dominika Siwik and Magdalena Gajewska and Dagmara Mirowska-Guzel and Iwona Kurkowska-Jastrzebska and Anna Czlonkowska and Marek Postula",
note = "Funding Information: Funding: E.C. was supported financially as part of the research grant {\textquoteleft}Preludium{\textquoteright} from the National Science Center, Poland (grant number 2017/25/N/NZ5/00545) and internal funding of the Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Centre for Preclinical Research and Technology CEPT, Warsaw, Poland. Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2022",
month = may,
day = "1",
doi = "10.3390/ijms23094530",
language = "English",
volume = "23",
journal = "International journal of molecular sciences",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "9",

}

RIS

TY - JOUR

T1 - Diagnostic Performance of Circulating miRNAs and Extracellular Vesicles in Acute Ischemic Stroke

AU - Eyileten, Ceren

AU - Jakubik, Daniel

AU - Shahzadi, Andleeb

AU - Gasecka, Aleksandra

AU - van der Pol, Edwin

AU - de Rosa, Salvatore

AU - Siwik, Dominika

AU - Gajewska, Magdalena

AU - Mirowska-Guzel, Dagmara

AU - Kurkowska-Jastrzebska, Iwona

AU - Czlonkowska, Anna

AU - Postula, Marek

N1 - Funding Information: Funding: E.C. was supported financially as part of the research grant ‘Preludium’ from the National Science Center, Poland (grant number 2017/25/N/NZ5/00545) and internal funding of the Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Centre for Preclinical Research and Technology CEPT, Warsaw, Poland. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022/5/1

Y1 - 2022/5/1

N2 - Background: Increased inflammation activates blood coagulation system, higher platelet activation plays a key role in the pathophysiology of ischemic stroke (IS). During platelet activation and aggregation process, platelets may cause increased release of several proinflammatory, and prothrombotic mediators, including microRNAs (miRNAs) and extracellular vesicles (EVs). In the current study we aimed to assess circulating miRNAs profile related to platelet function and inflammation and circulating EVs from platelets, leukocytes, and endothelial cells to analyse their diagnostic and predictive utility in patients with acute IS. Methods: The study population consisted of 28 patients with the diagnosis of the acute IS. The control group consisted of 35 age-and gender-matched patients on acetylsalicylic acid (ASA) therapy without history of stroke and/or TIA with established stable coronary artery disease (CAD) and concomitant cardiovascular risk factors. Venous blood samples were collected from the control group and patients with IS on ASA therapy (a) 24 h after onset of acute IS, (b) 7-days following index hospitalization. Flow cytometry was used to determine the concentration of circulating EVs subtypes (from platelets, leukocytes, and endothelial cells) in platelet-depleted plasma and qRT-PCR was used to determine several circulating plasma miRNAs (miR-19a-3p, miR-186-5p and let-7f). Results: Patients with high platelet reactivity (HPR, based on arachidonic acid-induced platelet aggregometry) had significantly elevated platelet-EVs (CD62+) and leukocyte-EVs (CD45+) concentration compared to patients with normal platelet reactivity at the day of 1 acute-stroke (p = 0.012, p = 0.002, respectively). Diagnostic values of baseline miRNAs and EVs were evaluated with receiver operating characteristic (ROC) curve analysis. The area under the ROC curve for miR-19a-3p was 0.755 (95% CI, 0.63–0.88) p = 0.004, for let-7f, it was 0.874 (95% CI, 0.76–0.99) p = 0.0001; platelet-EVs was 0.776 (95% CI, 0.65–0.90) p = 0.001, whereas for leukocyte-EVs, it was 0.715 (95% CI, 0.57–0.87) p = 0.008. ROC curve showed that pooling the miR-19a-3p expressions, platelet-EVs, and leukocyte-EVs concentration yielded a higher AUC than the value of each individual biomarker as AUC was 0.893 (95% CI, 0.79–0.99). Patients with moderate stroke had significantly elevated miR-19a-3p expression levels compared to patients with minor stroke at the first day of IS. (AUC: 0.867, (95% CI, 0.74–0.10) p = 0.001). Conclusion: Combining different biomarkers of processes underlying IS pathophysiology might be beneficial for early diagnosis of ischemic events. Thus, we believe that in the future circulating biomarkers might be used in the prehospital phase of IS. In particular, circulating plasma EVs and non-coding RNAs including miRNAs are interesting candidates as bearers of circulating biomarkers due to their high stability in the blood and making them highly relevant biomarkers for IS diagnostics.

AB - Background: Increased inflammation activates blood coagulation system, higher platelet activation plays a key role in the pathophysiology of ischemic stroke (IS). During platelet activation and aggregation process, platelets may cause increased release of several proinflammatory, and prothrombotic mediators, including microRNAs (miRNAs) and extracellular vesicles (EVs). In the current study we aimed to assess circulating miRNAs profile related to platelet function and inflammation and circulating EVs from platelets, leukocytes, and endothelial cells to analyse their diagnostic and predictive utility in patients with acute IS. Methods: The study population consisted of 28 patients with the diagnosis of the acute IS. The control group consisted of 35 age-and gender-matched patients on acetylsalicylic acid (ASA) therapy without history of stroke and/or TIA with established stable coronary artery disease (CAD) and concomitant cardiovascular risk factors. Venous blood samples were collected from the control group and patients with IS on ASA therapy (a) 24 h after onset of acute IS, (b) 7-days following index hospitalization. Flow cytometry was used to determine the concentration of circulating EVs subtypes (from platelets, leukocytes, and endothelial cells) in platelet-depleted plasma and qRT-PCR was used to determine several circulating plasma miRNAs (miR-19a-3p, miR-186-5p and let-7f). Results: Patients with high platelet reactivity (HPR, based on arachidonic acid-induced platelet aggregometry) had significantly elevated platelet-EVs (CD62+) and leukocyte-EVs (CD45+) concentration compared to patients with normal platelet reactivity at the day of 1 acute-stroke (p = 0.012, p = 0.002, respectively). Diagnostic values of baseline miRNAs and EVs were evaluated with receiver operating characteristic (ROC) curve analysis. The area under the ROC curve for miR-19a-3p was 0.755 (95% CI, 0.63–0.88) p = 0.004, for let-7f, it was 0.874 (95% CI, 0.76–0.99) p = 0.0001; platelet-EVs was 0.776 (95% CI, 0.65–0.90) p = 0.001, whereas for leukocyte-EVs, it was 0.715 (95% CI, 0.57–0.87) p = 0.008. ROC curve showed that pooling the miR-19a-3p expressions, platelet-EVs, and leukocyte-EVs concentration yielded a higher AUC than the value of each individual biomarker as AUC was 0.893 (95% CI, 0.79–0.99). Patients with moderate stroke had significantly elevated miR-19a-3p expression levels compared to patients with minor stroke at the first day of IS. (AUC: 0.867, (95% CI, 0.74–0.10) p = 0.001). Conclusion: Combining different biomarkers of processes underlying IS pathophysiology might be beneficial for early diagnosis of ischemic events. Thus, we believe that in the future circulating biomarkers might be used in the prehospital phase of IS. In particular, circulating plasma EVs and non-coding RNAs including miRNAs are interesting candidates as bearers of circulating biomarkers due to their high stability in the blood and making them highly relevant biomarkers for IS diagnostics.

KW - EVs

KW - ischemia

KW - let-7f

KW - leukocyte extracellular vesicles

KW - miR-186

KW - miR-19a

KW - platelet extracellular vesicles

KW - platelet reactivity

KW - prognosis

KW - stroke severity

UR - http://www.scopus.com/inward/record.url?scp=85128427363&partnerID=8YFLogxK

U2 - 10.3390/ijms23094530

DO - 10.3390/ijms23094530

M3 - Article

C2 - 35562921

VL - 23

JO - International journal of molecular sciences

JF - International journal of molecular sciences

SN - 1661-6596

IS - 9

M1 - 4530

ER -

ID: 24144102