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Published on: June 8, 2017
Circulating microRNAs reflect hemorrhagic MRI markers in cerebral amyloid angiopathy
J M G J Duijs1, E A Koemans2, N A Verwey3
1Department of Internal Medicine, Division of Nephrology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, the Netherlands.
Background:
Cerebral amyloid angiopathy is a major cause of intracerebral hemorrhage in older individuals. Although cerebral microbleeds (CMBs) and cortical superficial siderosis (cSS) aid MRI diagnosis they offer limited pathophysiological insight. MicroRNAs (miRs) regulate microvascular function and may serve as noninvasive biomarkers for distinguishing CAA subtypes and assessing hemorrhagic risk. This study investigated circulating miR profiles in probable CAA and Dutch-type hereditary CAA and examined their relationship with hemorrhagic MRI markers.
Methods:
Small RNA sequencing was performed on plasma from patients with probable CAA (n = 6) and symptomatic D-CAA (n = 6) compared to matched controls. Candidate miRs were validated by qPCR in a validation cohort of probable CAA patients (n = 20) and controls (n = 20). Bioinformatic analyses identified miR-mRNA interactions and pathway enrichment analysis. Correlation and receiver operating characteristic analyses evaluated the association with hemorraghic MRI-markers and the diagnostic performance of circulating plasma miRs.
Results:
Plasma miR-26b and miR-221 were significantly increased in probable CAA. MiR-26b, miR-221, miR-223, and miR-664a correlated with micro- and macrobleeds, with miR-26b showing the highest diagnostic accuracy (AUC 0.745). Target prediction highlighted genes involved in endothelial cell function including CDKN1B, FOXO1 and PTEN, with enrichment of NPAS4- and MECP2-related transcriptional pathways.
Conclusion:
Circulating miRs show potential as biomarkers reflecting hemorrhagic pathology in CAA.
