Mirnas profile in patients with brain arteriovenous malformation

Background: Brain arteriovenous malformation (BAVM) are vascular lesions described as anomalous tangle of vessels in which arteries and veins are directly connected without an intervening capillary system and normal brain tissue. When its presentation comes with vascular disrupt leads to serious neurological impairment or death. This feature can be directly associated to a biological molecular expression which can change the natural history of AVM. By this way a special focus on miRNA and its profile can explain the metabolic route to trace a diagnostic or a therapeutic biomarker.

Purposes: The authors showed up the epigenetic profile of BAVM in an Amazon folk as a hallmark to contribute to explain the main phenomena enrolled to cellullar, molecular and physiological processes in this disease.

Methods: We studied 22 patients (15 unruptured BAVM and 7 ruptured BAVM). The samples were analysed by Ultradeep Miseg platform (Ilumina) to achieve the study step-by-step in a sequence for small RNA. The reading was analysed using a packing DESq2 (program R) to appraise a distinguish expression of each miRNA. An analyzed was performed in garner sample using tools as: Target compare, miRtabase e TargetScan to establishnthe identity target genes from differential expressed miRNA.

Results: We identify 7 differential expressed miRNA (p adjusted < 0.05 and ILog2 [FoldChange]i>2), between normal controls and patients with brain AVM. From these miRNAs two were upregulated and 5 were downregulated. Of all miRNA found the most upregulated was hsa-miR-18a. Two miRNAs like as hsa-miR-17 and hsa-miR-19a-3p showed up a metabolic pathway influence regulating so many target genes such as: VCAM, SPRED1, PIK3R2, FZD4, LRP and JAK1. These genes are related to vascular remodeling, including angiogenesis and vasculogenesis. Also these genes achieve into extracellular matrix remodeling which is critical to pathophisiological mechanisms to Arteriovenous Malformation.

Conclusions: These is the first study which are outlined the Global miRNA profile about ruptured Brain AVM using a new generation of sequence research. This research showed up 7 new and discriminated miRNAs into ruptured brain AVM, suggesting a new enrollment.