Common and distinct circulating microRNAs in four neurovascular disorders

Area of Science:

• Neuroscience
• Genetics
• Biomarker Discovery

Background:

• Familial cerebral cavernous malformations (FCCM), Sturge-Weber Syndrome (SWS), and hereditary hemorrhagic telangiectasia (HHT) are genetic disorders causing vascular abnormalities and brain bleeding risk.
• Cerebral microbleeds (CMBs) are linked to aging, with less understood genetic influences.
• Circulating microRNAs (miRNAs) are investigated as potential biomarkers reflecting disease mechanisms.

Purpose of the Study:

• To identify common and distinct circulating microRNAs (miRNAs) in FCCM, SWS, HHT, and CMB.
• To explore the mechanistic pathways associated with these miRNAs.
• To assess the potential of miRNAs as clinical biomarkers for neurovascular disorders.

Main Methods:

• Plasma samples from patients with FCCM, SWS, HHT, CMB, and healthy controls were analyzed for differentially expressed (DE) miRNAs.
• Ingenuity Pathway Analysis and transcriptome integration identified gene targets and pathways.
• Quantitative real-time PCR (ddPCR) validated selected DE miRNAs.

Main Results:

• Significant differences in plasma miRNA expression were found across all studied neurovascular conditions compared to controls.
• Eighteen DE miRNAs were commonly dysregulated in at least two of the disorders.
• The PI3K-Akt and ROBO SLIT signaling pathways were consistently identified across all four conditions.
• Validation confirmed the differential expression of four key miRNAs.

Conclusions:

• Commonly dysregulated miRNAs highlight shared underlying mechanisms in neurovascular disorders.
• These miRNAs show promise for further mechanistic research and potential clinical applications in disease monitoring and treatment.