ABSTRACT Among cerebrovascular malformations, brain arteriovenous malformation (bAVM) and cerebral cavernous malformation (CCM) primarily affect microvessels. Brain AVM originates from arterioles due to impaired expression of endothelial differentiation markers, whereas CCM arises due to aberrant sprouting angiogenesis. Recent advances in the field of lncRNAs have linked perturbations of the competitive endogenous RNA (ceRNA) lncRNA–miRNA–mRNA axis to the development of several pathological conditions. However, this mechanism remains poorly investigated in cerebrovascular phenotypes. Based on RNA‐seq data and enrichment analysis, we identified lncRNA genes differentially expressed in endothelial cells (ECs) isolated from bAVM and CCM biopsies. We isolated RNA from both ECs and blood samples of larger patient cohorts. By quantitative real‐time PCR, gene expression was compared between pathological ECs and human brain microvascular endothelial cells (HBMECs) and between blood samples of patients and healthy controls. We identified five lncRNA genes, MIR497HG , RMST , SNHG6 , SOX2‐OT , and ZSCAN16‐AS1 overexpressed in both ECs and blood samples of bAVM patients. In CCM ECs, FGD5‐AS1 and SNHG12 were upregulated and XIST , NORAD , SNHG29 , and LINC0066 down‐expressed. These lncRNAs act as molecular sponges for miRNAs targeting transcripts associated with the onset of the respective phenotypes. Specifically, arteriovenous differentiation and vascular smooth muscle cell function were the two most enriched pathways related to the bAVM phenotype. For the CCM condition, the most enriched pathways included Rho‐GTPase, Delta‐Notch, and VEGF signalling. These data suggest a novel investigation field to better elucidate the differences in the pathogenesis, differential diagnosis, and potential therapeutic strategies for bAVM and CCM phenotypes.
Mordà et al. (Thu,) studied this question.