Editome landscape of CCM-derived endothelial cells

m6A modifications of circular RNAs in ischemia-induced retinal neovascularization

“…GO analysis based on the 84 mRNAs involved showed that the majority of the enriched genes were involved in cellular process, cellular anatomical entity, and binding (Figure 6 A); indicating the potential importance of m 6 A-modified circRNAs in retinal neovascularization. Recent studies showed the involvement of RNA editing modifications in retinal and vascular pathogenesis 33 , 34 , which indicated that the differential edited genes were enriched in pathways associated with angiogenesis, inflammation and apoptosis. It is also interesting to conduct the integrated analysis of multi-omics of the m 6 A methylation with other kinds of RNA modifications to further explore the cellular mechanisms in ischemia-induced retinopathy.…”

Remodeling of the Neurovascular Unit Following Cerebral Ischemia and Hemorrhage

“…A study of sporadic human CCM lesions identified differential editing events pertaining to CCM-ECs compared with human brain microvasculature endothelial cells (HBMECs) via whole RNA sequencing data. They found that out of the 60% of genes that were edited in both HBMECs and CCM-ECs, greater than 37% of them were totally lost in CCM-ECs while 30% of them were partially lost [ 336 ]. Many of these differentially edited genes encode for proteins that are involved in pathways related to cell adhesion, angiogenesis, apoptosis, cell survival and cytoskeleton regulation [ 336 , 337 ].…”

“…They found that out of the 60% of genes that were edited in both HBMECs and CCM-ECs, greater than 37% of them were totally lost in CCM-ECs while 30% of them were partially lost [ 336 ]. Many of these differentially edited genes encode for proteins that are involved in pathways related to cell adhesion, angiogenesis, apoptosis, cell survival and cytoskeleton regulation [ 336 , 337 ]. Notably, large clusters of genes involved in inflammatory pathways were enriched in CCM-ECs.…”

“…The proteins these genes encode for are involved in many angiogenic-related pathways and the maintenance of EC homeostasis, including apoptosis, cell-ECM adhesion, hypoxia response, and oxidative stress response [ 337 ]. However, it should be noted that both individuals with the inherited form of the disease and those without lesions can have an absence of germline and somatic mutations at the three CCM loci [ 336 , 337 ], pointing to further genetic factors contributing to the pathogenesis and progression of CCMs. Deep location (brainstem, cerebellar nuclei, thalamus, or basal ganglia) appears to be the most important predictor of subsequent hemorrhage of CCMs [ 353 ].…”