RNA profiling of sEV (small extracellular vesicles)/exosomes reveals biomarkers and vascular endothelial dysplasia with moyamoya disease

Abstract

The association of exosomal RNA profiling and pathogenesis of moyamoya disease (MMD) and intracranial Atherosclerotic disease (ICAD) is unknown. In this study, we investigated the RNA profiles of sEV (small extracellular vesicles)/exosomes in patients with MMD and ICAD. Whole blood samples were collected from 30 individuals, including 10 patients with MMD, 10 patients with ICAD, and 10 healthy individuals. Whole transcriptome analysis was performed using the GeneChip WT Pico Reagent kit. Transcriptional correlation was verified using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The association between functional dysregulation and candidate RNAs was studied in vitro. In total, 1,486 downregulated and 2,405 upregulated RNAs differed significantly between patients with MMD and healthy controls. Differential expression of six circRNAs was detected using qPCR. Among these significantly differentially expressed RNAs, IPO11 and PRMT1 circRNAs were upregulated, whereas CACNA1F circRNA was downregulated. This is the first study showing that the differential expression of exosomal RNAs associated with MMD pathogenesis, such as overexpression of IPO11 and PRMT1 circRNAs, may be related to angiogenesis in MMD. The downregulation of CACNA1F circRNA may be related to vascular occlusion. These results propose the utility of exosomal RNAs as biological markers in MMD.

Identification of oxidative phosphorylation-related genes in moyamoya disease by combining bulk RNA-sequencing analysis and machine learning

“…Cao et al found that activin receptor-like kinase 7 promotes VSMC apoptosis by activating the Smad2/3 signaling in diabetic atherosclerosis ( Cao et al, 2022 ). These studies provided evidence that SMAD2 downregulation in patients with MMD might promote angiogenesis, proliferation and phenotype switching of VSMCs, which are the important characteristics of MMD mentioned before ( Ma et al, 2022 ; He et al, 2023c ; He et al, 2023d ). As for the results in our study, pathway enrichment analysis also showed that SMAD2 was enriched in the Notch, GAP junction, and toll-like receptor signaling pathways, which are also associated with angiogenesis, vascular development, endothelial cell and VSMC growth in previous studies ( Beyer and Berthoud, 2018 ; Shafeghat et al, 2022 ; Cuervo et al, 2023 ).…”

Multiomics and blood-based biomarkers of moyamoya disease: protocol of Moyamoya Omics Atlas (MOYAOMICS)

“…Previous research has provided valuable insights into the distinct patterns of exosomal RNA expression that are associated with the pathogenesis of MMD [ 17 ]. Specifically, the upregulation of IPO11 and PRMT1 circRNAs has been linked to the promotion of angiogenesis in MMD, while the underexpression of CACNA1F circRNA is associated with vascular occlusion.…”