Circulating miRNA profiles and the risk of hemorrhagic transformation after thrombolytic treatment of acute ischemic stroke: a pilot study

Marcin Stańczak; Adam Wyszomirski; Paulina Słonimska; Barbara Kołodziej; Bartosz Jabłoński; Anna Stanisławska-Sachadyn; Bartosz Karaszewski

doi:10.3389/fneur.2024.1399345

Circulating miRNA profiles and the risk of hemorrhagic transformation after thrombolytic treatment of acute ischemic stroke: a pilot study

Front Neurol. 2024 Jun 12:15:1399345. doi: 10.3389/fneur.2024.1399345. eCollection 2024.

Authors

Marcin Stańczak^{1

2}, Adam Wyszomirski³, Paulina Słonimska⁴, Barbara Kołodziej³, Bartosz Jabłoński^{1

2}, Anna Stanisławska-Sachadyn^{5

6}, Bartosz Karaszewski^{1

2

3}

Affiliations

¹ Department of Adult Neurology, Faculty of Medicine, Medical University of Gdańsk, Gdańsk, Poland.
² Department of Adult Neurology, University Clinical Center, Gdańsk, Poland.
³ Brain Diseases Centre, Medical University of Gdańsk, Gdańsk, Poland.
⁴ Laboratory for Regenerative Biotechnology, Department of Biotechnology and Microbiology, Gdańsk University of Technology, Gdańsk, Poland.
⁵ Department of Biotechnology and Microbiology, Gdańsk University of Technology, Gdańsk, Poland.
⁶ BioTechMed Center, Gdańsk University of Technology, Gdańsk, Poland.

Abstract

Background: Hemorrhagic transformation (HT) in acute ischemic stroke is likely to occur in patients treated with intravenous thrombolysis (IVT) and may lead to neurological deterioration and symptomatic intracranial hemorrhage (sICH). Despite the complex inclusion and exclusion criteria for IVT and some useful tools to stratify HT risk, sICH still occurs in approximately 6% of patients because some of the risk factors for this complication remain unknown.

Objective: This study aimed to explore whether there are any differences in circulating microRNA (miRNA) profiles between patients who develop HT after thrombolysis and those who do not.

Methods: Using qPCR, we quantified the expression of 84 miRNAs in plasma samples collected prior to thrombolytic treatment from 10 individuals who eventually developed HT and 10 patients who did not. For miRNAs that were downregulated (fold change (FC) <0.67) or upregulated (FC >1.5) with p < 0.10, we investigated the tissue specificity and performed KEGG pathway annotation using bioinformatics tools. Owing to the small patient sample size, instead of multivariate analysis with all major known HT risk factors, we matched the results with the admission NIHSS scores only.

Results: We observed trends towards downregulation of miR-1-3p, miR-133a-3p, miR-133b and miR-376c-3p, and upregulation of miR-7-5p, miR-17-3p, and miR-296-5p. Previously, the upregulated miR-7-5p was found to be highly expressed in the brain, whereas miR-1, miR-133a-3p and miR-133b appeared to be specific to the muscles and myocardium.

Conclusion: miRNA profiles tend to differ between patients who develop HT and those who do not, suggesting that miRNA profiling, likely in association with other omics approaches, may increase the current power of tools predicting thrombolysis-associated sICH in acute ischemic stroke patients. This study represents a free hypothesis-approach pilot study as a continuation from our previous work. Herein, we showed that applying mathematical analyses to extract information from raw big data may result in the identification of new pathophysiological pathways and may complete standard design works.

Keywords: biomarker; hemorrhagic transformation; ischemic stroke; miR; microRNA; thrombolysis.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This research was Funded by Siemens Helthineers (research grant for the Medical University of Gdansk, PI—BKa, 2018; Contract Number C00229230), by the Excellence Initiative – Research University program at the Medical University of Gdansk and by the Medical University of Gdansk.