VPB1298 - Platelet-derived miRNAs and platelet-derived extracellular vesicles as emerging diagnostic and prognostic biomarkers in acute ischemic stroke patients

Tuesday, July 12, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: Virtual

Presenting Author(s)

CE

Ceren Eyileten

Senior Researcher
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, 02-091 Warsaw, Poland
Warsaw, Mazowieckie, Poland

Co-Author(s)

DJ

Daniel Jakubik

PhD candidate
Medical University of Warsaw
Warsaw, Mazowieckie, Poland
AS

Andleeb Shahzadi

Assistant Prof
Istanbul Cerrahpasa University
Istanbul, Istanbul, Turkey
JJ

Joanna Jarosz-Popek

PhD candidate
Medical University of Warsaw
Warsaw, Mazowieckie, Poland
DK

Disha Keshwani

Student
1. Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, 02-091 Warsaw, Poland
Warsaw, Mazowieckie, Poland
AG

Aleksandra Gasecka

Assistant Prof
Medical University of Warsaw
Warsaw, Mazowieckie, Poland
MW

Marta Wolska

PhD candidate
Medical University of Warsaw
warsaw, Mazowieckie, Poland
AN

Anna Nowak

PhD candidate
Medical University of Warsaw
Warsaw, Mazowieckie, Poland
SD

Salvatore De Rosa

Prof
Magna Graecie University
Catanzaro, Calabria, Italy
Ev

Edwin van der Pol

Assistant Prof
University of Amsterdam
Amsterdam, Noord-Holland, Netherlands
DM

Dagmara Mirowska-Guzel

Prof
Medical University of Warsaw
Warsaw, Mazowieckie, Poland
IK

Iwona Kurkowska-Jastrzebska

Prof
Institute of Psychiatry and Neurology
Warsaw, Mazowieckie, Poland
AC

Anna Członkowska

Professor, MD
2nd Department of Neurology, Institute of Psychiatry and Neurology
Warszawa, Mazowieckie, Poland

Background: Ischemic stroke (IS) is one of the most frequent causes of death.

Aims: We aimed to analyze the circulating platelet-derived miR-19a-3p, miR-186-5p, Let-7f, platelet-extracellular vesicles (EVs), leukocyte-EVs, and endothelial-EVs levels 24-h and 7-days after IS as novel diagnostic and prognostic/predictive biomarkers.

Methods: Blood samples of 28 patients with acute IS were collected 24-h and 7-days after stroke and 35 age- and gender-matched individuals free of stroke. Platelet reactivity by AA-, TRAP-, ADP-induced platelet aggregometry. PlasmaRNA was extracted; quality RNA was assessed: fluorometric assay; RT-PCR for miRNAs expression and flow-cytometry for EVs determination.

Results: Patients with IS on day-1 had significantly higher platelet reactivity assessed by AA-induced platelet aggregometry compared to controls (p=0.001). Patients with normal platelet activation had significantly higher miR-186-5p expression levels compared to patients with HPR at day-1 acute-stroke (p=0.034). 7-days after stroke, expression levels of miR-186-5p decreased in the same patients with normal platelet reactivity (p=0.036). Patients with HPR had significantly elevated platelet-EVs (CD62) concentration compared to patients with normal platelet reactivity at the day of 1 acute-stroke (p=0.012). Patients with HPR had significantly higher leukocyte-EVs (CD45) concentration compared to patients with normal platelet function at day-1 stroke (p=0.002). Diagnostic values of baseline miRNAs and EVs were evaluated with receiver operating characteristic curve analysis. 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 compared to patients with minor stroke at the day of acute IS. ROC curve was 0.867, (95% CI, 0.74-0.10) p=0.001.

Conclusion(s): Our analysis showed alteration of circulating miRNAs and EVs after IS. Combination of miR-19a-3p, Let-7f, platelet-EVs and leukocyte-EVs might have a diagnostic value for acute stroke and miR-19a-3p can predict the severity of stroke in IS patients.