Metabolomic signatures associated with pathological angiogenesis in moyamoya disease

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 ).…”

“…Previous studies have demonstrated that OXPHOS is related to abnormal EC, VSMC, and angiogenesis, which might play important roles in vascular disease pathogenesis. As a cerebral vascular disease, the pathological characteristics of MMD also includes abnormal EC proliferation, abnormal VSMC migration, pathological angiogenesis, and vascular remodeling ( Takagi et al, 2016 ; He et al, 2023b ; He et al, 2023c ). This generates evidence that OXPHOS disorder or regulation is closely related to MMD mechanism.…”

Multi‐omic approaches for biomarker discovery in Moyamoya disease

“…2 Since the challenging sampling of cerebral artery specimens for transcriptomic studies, other ultrasensitive techniques were recently carried out for molecular profiling of circulating biomarkers from cerebrospinal fluid (CSF) or blood. The study by Ota et al through a F I G U R E 1 Summary of the multi-omic approaches and results reported by He et al 10 Haemorrhagic stroke (HS), healthy control (HC), ischemic stroke (IS), lysophosphatidylcholine (LPC), LPCAT4 (lysophosphatidylcholine acyltransferase 4), major facilitator superfamily domain-containing protein 2 (MFSD2A), middle cerebral artery (MCA), moyamoya disease (MMD), phospholipase A1 member A (PLA1A), PLA2G2A (phospholipase A2 group IIA) and superficial temporal artery (STA). (Created with BioRender.com).…”

“…More recently, He and colleagues reported a comprehensive and detailed multi-omics analysis of MMD molecular profiles, including genomics (whole-exome sequencing), transcriptomics (RNA-seq) and metabolomics (ultra-high-performance LC-high-resolution MS, UHPLC-HRMS) approaches (Figure 1). 10 Notably, the untargeted metabolomics suggested lysophosphatidylcholine (i.e. LPC 16:1-2) as potential diagnostic blood (i.e.…”

“…In addition, combining multiple omics strategies may also shed light on potential novel targets for MMD therapeutic intervention, as shown above for FLNA and LPC. 6,7,10…”