实验性自身免疫性脑脊髓炎
血管生成
神经炎症
多发性硬化
转录组
血管内皮生长因子
新生血管
胶质瘤
免疫系统
小胶质细胞
免疫学
病理
癌症研究
体内
脑脊髓炎
医学
生物
炎症
血管内皮生长因子受体
基因表达
生物化学
基因
生物技术
作者
Sanjid Shahriar,Saptarshi Biswas,Kuaile Zhao,Uğur Akcan,Mary Claire Tuohy,Michael Glendinning,A M Kurt,Charlotte R. Wayne,Grace Prochilo,Marvin Price,Rolf A. Brekken,Vilas Menon,Dritan Agalliu
标识
DOI:10.1101/2022.11.15.516660
摘要
ABSTRACT Histopathological studies of multiple sclerosis (MS), a demyelinating disease of the central nervous system (CNS), and its animal model, experimental autoimmune encephalomyelitis (EAE), have found newly formed leaky vessels in demyelinated acute and chronic plaques, in addition to blood-brain barrier (BBB) damage in existing vessels, that exacerbate disease pathology by increasing infiltration of immune cells. Which vessel subtypes and signaling pathways generate these aberrant vessels is poorly understood. Using single-cell RNA-sequencing and in vivo validation, we find that transcriptome signatures of neo-angiogenesis arise in venous endothelial cells in both acute and chronic EAE, and correlate with upregulation in VEGF-A signaling. These neo-angiogenic markers are also increased in acute and chronic MS lesions. Treatment with a VEGF-A blocking antibody diminishes neo-angiogenic transcriptomic signatures and vascular proliferation in vivo , but does not restore BBB function or ameliorate significantly EAE pathology. Therefore, anti-angiogenic therapies in combination with immunomodulatory therapies may benefit MS progression.
科研通智能强力驱动
Strongly Powered by AbleSci AI