Plasma extracellular vesicle-associated miR-512-3p modulates angiogenesis in pediatric Moyamoya disease by targeting ARHGEF3

• Published in: Scientific reports Vol. 15; no. 1; pp. 24655 - 14
• Main Authors: Koh, Eun Jung, Choi, Seung Ah, Moon, Youn Joo, Lee, Heeyoung, Phi, Ji Hoon, Kim, Seung-Ki
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.07.2025; Nature Publishing Group; Nature Portfolio
• Subjects: 631/337; 631/80; 692/53; 692/699; Adolescent; Angiogenesis; ARHGEF3; Bioinformatics; Biomarkers; Biopsy; Case-Control Studies; Cell viability; Cerebrovascular diseases; Child; Child, Preschool; Chronic illnesses; Colony-forming cells; Disease; Endothelial Cells - metabolism; Endothelial colony-forming cells; Extracellular vesicles; Extracellular Vesicles - genetics; Extracellular Vesicles - metabolism; Female; Guanine nucleotide exchange factor; Guanosine triphosphatases; Humanities and Social Sciences; Humans; Immunoblotting; Male; Medical imaging; MicroRNAs; MicroRNAs - blood; MicroRNAs - genetics; MicroRNAs - metabolism; MiR-512-3p; miRNA; Moyamoya disease; Moyamoya Disease - blood; Moyamoya Disease - genetics; Moyamoya Disease - metabolism; Moyamoya Disease - pathology; multidisciplinary; Nanoparticles; Neovascularization, Pathologic - genetics; Pediatrics; Plasma; Proteins; Rho Guanine Nucleotide Exchange Factors - genetics; Rho Guanine Nucleotide Exchange Factors - metabolism; rhoA GTP-Binding Protein - metabolism; RhoA protein; Science; Science (multidisciplinary); Transmission electron microscopy; Vascular diseases; Veins & arteries; Palo Alto California; United States > US; South Korea; Extracellular vesicles; ARHGEF3; Endothelial colony-forming cells; Moyamoya disease; MiR-512-3p
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-025-08796-4

Moyamoya disease (MMD) is a chronic cerebrovascular disorder and a leading cause of pediatric stroke. Extracellular vesicles (EVs) carrying microRNAs (miRNAs) play a pivotal role in intercellular communication within cerebrovascular diseases. This study aimed to identify specific miRNAs within plasma-derived EVs from MMD patients and investigate their functional implications. Study subjects included healthy controls ( N  = 13) and MMD patients ( N  = 23). EVs were isolated from plasma samples and characterized by transmission electron microscopy, nanoparticle tracking analysis, ExoView, RT-qPCR, and immunoblotting. miRNA profiles were assessed through NanoString analysis. Functional effects of miR-512-3p inhibition were evaluated in MMD endothelial colony-forming cells (ECFCs) by analyzing guanosine triphosphatase (GTPase) activity, tubule formation, and cell viability. MMD-derived EVs exhibited an upregulation of miR-512-3p compared to controls. Bioinformatics analysis identified RHO guanine nucleotide exchange factor 3 (ARHGEF3) as a potential target of miR-512-3p. Inhibition of miR-512-3p in MMD ECFCs resulted in increased expression of ARHGEF3 and its downstream effector RHOA, leading to enhanced GTPase activity and improved tubule formation, indicative of restored angiogenic function. Elevated levels of miR-512-3p within plasma-derived EVs may serve as a novel biomarker for MMD diagnosis. The modulation of ARHGEF3 and subsequent RHOA signaling by targeting miR-512-3p contributes to the dysregulated angiogenesis in MMD.