Understanding the pathogenesis of brain arteriovenous malformation: genetic variations, epigenetics, signaling pathways, and immune inflammation

AbstractBrain arteriovenous malformation (BAVM) is a rare but serious cerebrovascular disease whose pathogenesis has not been fully elucidated. Studies have found that epigenetic regulation, genetic variation and their signaling pathways, immune inflammation, may be the cause of BAVM the main reason. This review comprehensively analyzes the key pathways and inflammatory factors related to BAVMs, and explores their interplay with epigenetic regulation and genetics. Studies have found that epigenetic regulation such as DNA methylation, non-coding RNAs and m6A RNA modification can regulate endothelial cell proliferation, apoptosis, migration and damage repair of vascular malformations through different target gene pathways. Gene defects such asKRAS,ACVRL1 andEPHB4 lead to a disordered vascular environment, which may promote abnormal proliferation of blood vessels through ERK, NOTCH, mTOR, Wnt and other pathways.PDGF-B andPDGFR- β were responsible for the recruitment of vascular adventitial cells and smooth muscle cells in the extracellular matrix environment of blood vessels, and played an important role in the pathological process of BAVM. Recent single-cell sequencing data revealed the diversity of various cell types within BAVM, as well as the heterogeneous expression of vascular-associated antigens, while neutrophils, macrophages and cytokines such as IL-6, IL-1, TNF- α, and IL-17A in BAVM tissue were significantly increased. Currently, there are no specific drugs targetin...
Source: Human Genetics - Category: Genetics & Stem Cells Source Type: research