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Inflammatory Responses Induced by the Rupture of Intracranial Aneurysms Are Modulated by miRNAs

Michal Korostynski1, Rafal Morga2, Marcin Piechota1

  • 1Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, ul. Smetna 12, 31-343, Krakow, Poland.

Molecular Neurobiology
|October 27, 2019
PubMed

Insights

Intracranial aneurysm rupture significantly alters microRNA (miRNA) expression in blood cells, impacting immune responses. These findings shed light on the molecular mechanisms behind the inflammatory cascade following aneurysm rupture.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • The molecular consequences of intracranial aneurysm (IA) rupture, particularly concerning microRNA (miRNA) expression in peripheral blood, are not well understood.
  • Investigating these changes is crucial for comprehending the systemic inflammatory response post-rupture.

Purpose of the Study:

  • To characterize the differential expression of miRNAs in peripheral blood cells following IA rupture.
  • To explore the functional implications and target interactions of these dysregulated miRNAs.
  • To correlate miRNA changes with specific inflammatory markers at the mRNA and protein levels.

Main Methods:

  • Deep transcriptome sequencing of small RNAs from patients in acute (0-72h) and chronic (3-15 months) phases post-IA rupture, compared to controls.
  • Bioinformatic analysis for identifying differentially expressed miRNAs and their predicted target genes.
  • Functional pathway analysis (e.g., cytokine-cytokine receptor interactions).
  • Validation of target gene expression at mRNA and protein levels, focusing on inflammatory factors like HMGB1 and FASLG.

Main Results:

  • 106 mature miRNAs and 90 miRNA precursors showed differential expression between patient groups and controls.
  • Top affected pathways included cytokine-cytokine receptor interactions, indicating a strong inflammatory component.
  • Identified miRNAs targeted key inflammatory mediators, including HMGB1 and FASLG, with corresponding changes observed at mRNA and protein levels.
  • Significant alterations in peripheral blood cell transcription profiles were evident post-IA rupture.

Conclusions:

  • Intracranial aneurysm rupture profoundly impacts miRNA expression in peripheral blood cells.
  • The dysregulated miRNAs are implicated in the regulation of immune cell homeostasis and inflammatory responses.
  • These findings provide insights into the molecular mechanisms governing the inflammatory response to IA rupture and may inform future diagnostic or therapeutic strategies.
Keywords:
CytokinesIntracranial aneurysmPeripheral bloodSubarachnoid hemorrhagemiRNA

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