Background: Cerebral vasospasm (CVS) is a major determinant of prognosis in patients with subarachnoid hemorrhage (SAH). Alteration in the vascular phenotype contributes to development of CVS. However, little is known about the role of microRNAs (miRNAs) in the phenotypic alteration after SAH. We investigated the expression profile of miRNAs and the chronological changes in the expression of microRNA-15a (miR-15a) and Kruppel-like factor 4 (KLF4), a potent regulator of vascular phenotype modulation that modulates the expression of miR-15a, in the plasma and cerebrospinal fluid (CSF) of SAH patients.
Methods: Peripheral blood and CSF samples were collected from eight aneurysmal SAH patients treated with endovascular obliteration. Samples obtained from three patients without SAH were used as controls in the analysis. Exosomal miRNAs were isolated and subjected to microarray analysis with the 3D-gene miRNA microarray kit. The time course of the expression of miR-15a and KLF4 was analyzed using quantitative real-time PCR.
Results: Microarray analysis demonstrated that 12 miRNAs including miR-15a were up- or down-regulated both in the CSF and plasma after SAH within three days. Quantitative real-time PCR revealed that miR-15a expression was significantly increased in both the CSF and plasma, with a peak around 3 to 5 days after SAH, whereas the expression of KLF4 was significantly decreased around 1 to 3 days after SAH and remained lower than in controls.
Conclusion: Our results suggest that an early and persistent decrease in KLF4 followed by an increase in miR-15a may contribute to the altered vascular phenotype, resulting in development of CVS.