Circulating microRNAs Associated With Reversible Cerebral Vasoconstriction Syndrome

Area of Science:

• Neuroscience
• Genetics
• Molecular Biology

Background:

• Reversible cerebral vasoconstriction syndrome (RCVS) is a neurological condition characterized by temporary narrowing of brain arteries.
• Understanding the molecular mechanisms underlying RCVS pathogenesis is crucial for developing effective diagnostic and therapeutic strategies.

Purpose of the Study:

• To investigate the role of circulating microRNAs (miRNAs) in the pathogenesis of reversible cerebral vasoconstriction syndrome (RCVS).

Main Methods:

• Prospective recruitment of three independent patient cohorts with RCVS and matched controls.
• Next-generation small RNA sequencing and quantitative polymerase chain reaction (PCR) for miRNA identification and validation.
• In vitro functional analysis and computational prediction of miRNA target genes and pathways.

Main Results:

• A panel of miRNAs (miR-130a-3p, miR-130b-3p, let-7a-5p, let-7b-5p, let-7f-5p) differentiated RCVS patients from controls with high accuracy (AUC > 0.86).
• Specific let-7 miRNAs were elevated in acute migraine, suggesting a link to inflammatory or vascular processes.
• Functional studies indicated that these miRNAs, particularly miR-130a-3p, are involved in regulating the transforming growth factor-β signaling pathway, endothelin-1, and blood-brain barrier (BBB) integrity.

Conclusions:

• Circulating miRNA signatures are associated with RCVS.
• These miRNAs may be functionally linked to RCVS-related symptoms such as headache, BBB disruption, and impaired vasomotor function.