Center for Cerebrovascular Research, University of California, San Francisco, CA 94143, USA.
Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA 94143, USA.
Cells. 2024 Jan 1;13(1):92. doi: 10.3390/cells13010092.
The increase in the collagen I (COL I)/COL III ratio enhances vessel wall stiffness and renders vessels less resistant to blood flow and pressure changes. Activated microglia enhance inflammation-induced fibrosis. The COL I/COL III ratio in human and mouse brain arteriovenous malformations (bAVMs) is associated with bAVM hemorrhage, and the depletion of microglia decreases the COL I/COL III ratio and hemorrhage. COL I, COL III, and hemorrhages were analyzed in 12 human bAVMs and 6 control brains, and mouse bAVMs induced in three mouse lines with activin receptor-like kinase 1 ( = 7) or endoglin ( = 7) deleted in the endothelial cells or brain focally ( = 5). The controls for the mouse study were no-gene-deleted litter mates. Mouse bAVMs were used to test the relationships between the Col I/Col III ratio and hemorrhage and whether the transient depletion of microglia reduces the Col I/Col III ratio and hemorrhage. The COL I/COL III ratio was higher in the human and mouse bAVMs than in controls. The microhemorrhage in mouse bAVMs was positively correlated with the Col I/Col III ratio. Transient depletion of microglia reduced the Col I/Col III ratio and microhemorrhage. The COL I/COL III ratio in the bAVMs was associated with bAVM hemorrhage. The depletion of microglia reduced the bAVM Col I/Col III ratio and hemorrhage.
I 型胶原（COL I）/III 型胶原（COL III）比值的增加会增强血管壁的僵硬程度，使血管对血流和压力变化的抵抗力降低。活化的小胶质细胞增强炎症诱导的纤维化。人类和小鼠脑动静脉畸形（bAVM）中的 COL I/COL III 比值与 bAVM 出血有关，小胶质细胞耗竭会降低 COL I/COL III 比值并减少出血。分析了 12 个人类 bAVM 和 6 个对照脑，以及在三种小鼠品系中诱导的小鼠 bAVM，这些小鼠品系中的激活素受体样激酶 1（ = 7）或内皮细胞（ = 7）或大脑局部（ = 5）缺失。小鼠研究的对照是没有基因缺失的同窝仔鼠。使用小鼠 bAVM 来测试 Col I/Col III 比值与出血之间的关系，以及短暂耗尽小胶质细胞是否会降低 Col I/Col III 比值和出血。COL I/COL III 比值在人类和小鼠 bAVM 中均高于对照。小鼠 bAVM 中的微出血与 Col I/Col III 比值呈正相关。短暂耗尽小胶质细胞会降低 Col I/Col III 比值和微出血。bAVM 中的 COL I/COL III 比值与 bAVM 出血有关。小胶质细胞耗竭会降低 bAVM 的 Col I/Col III 比值和出血。
