Roles of macrophages in intracranial aneurysm / 国际脑血管病杂志

Inflammation plays a key role in the formation of intracranial aneurysm. At present, the pathophysiological processes of intracranial aneurysms are mainly caused by both hemodynamic abnormalities and inflammation. Studies have shown that the inflammatory cels in the intracranial aneurysm wal are mainly mononuclear macrophages, and can secrete various effector molecules, weakening and destroying the structures of the vessel wal . Therefore, the research of the roles of differences played in different subtypes of macrophages and their effector molecules in the pathophysiological processes of intracranial aneurysms wil provide clues for exploring the pathogenesis of intracranial aneurysms and effective targeted therapy.

Role of P120 catenin in the endothelial cells injury induced by an impinging flow / 中国脑血管病杂志

Objective To investigate the role and possible mechanism of P120 catenin involving in the hemodynamic changes by inducing vascular endothelial cells injury through an in vitro experiment. Methods The hemodynamic environment under the different hemodynamic conditions at the vascular bifurcations was simulated through a T-shaped flow chamber system designed by ourselves. The human umbilical vein endothelial cells (HUVEC)cultured in vitro were stimulated and used the HUVEC cells of the small interfering RNA (SiRNA)after P120ctn gene fragments being knocked out. After loading flow rate of 250 and 500 ml/ min respectively and acting on for 12 h,the HUVEC morphology,growth pattern,and expression of P120ctn and other proteins were observed. Results (1)Normal HUVEC:500 ml/ min was loaded for 12 h,the cells were fused excessively at the impinging point,the cell gaps became narrowed,the cell density decreased and the morphology was elongated in the high wall shear stress (WSS)and wall shear stress gradient (WSSG)regions. A part of cells migrated downstreamly,and their arrangement direction was consistent with the direction of impinging flow. Compared with the unloaded impinging flow field,after the 2 kinds of impinging flows being loaded for 12 h,the expression levels of P120ctn,vascular endothelial calcium (VEC),Kaiso,α-catenin,and other proteins were decreased. The expression level of matrix metalloproteinase 2 (MMP-2)was increased. There were significant differences (all P < 0. 05). (2)HUVEC after P120ctn being knocked out:Under the impact of the impinging flow,the cell growth time was reduced to 60 min. 250 ml/ min being loaded for 60 min,the impinging point and its surrounding cells still maintained the polygon,but some cells in the high WSS and high WSSG regions began to move downstreamly and aggregated,the cell arrangement mode partly arranged along with the direction of the flow;500 ml / min being loaded for 60 min,the cell density in the high WSS and high WSSG regions were decreased significantly and the morphology was elongated. A large number of cells migrated downstreamly and aggregated. The arrangement mode was parallel and consistent with the direction of the impinging flow. Compared with the unloaded impinging flow field,after the 2 kinds of velocities being loaded for 60 min,the expression levels of VEC,Kaiso,α-catenin proteins were decreased. The expression level of MMP-2 was increased,There were significant differences (all P < 0. 05) Conclusions The hemodynamic change may induce the changes in vascular endothelial cell morphology,growth pattern,and expression of P120ctn and other related proteins, leading to the decrease of vascular endothelial cell adhesion connection stability and the expression changes of related proinflammatory factors. The knockout of P120ctn may result in a further decrease of the vascular endothelial cell adhesion connection stability.