To explore the mechanism of AGEs on diabetic endothelial cell damage based on monocyte⁃macrophage exosomes/microRNA⁃92a / 安徽医科大学学报
Acta Universitatis Medicinalis Anhui
; (6): 85-94, 2023.
Article
в Zh
| WPRIM
| ID: wpr-1036484
Ответственная библиотека:
WPRO
ABSTRACT
Objective@#To explore the mechanism of advanced glycation end products (AGEs) on diabetic endothelial cell damage based on monocyte⁃macrophage exosomes (Exos)/microRNA⁃92a ( miR⁃92a) .@*Methods@#Twenty apolipoprotein E ⁃deficient (ApoE - / - ) mice were randomly divided into two groups injury group (n = 10) and injury + STZ group ( n = 10 ) . The injury + STZ group established a diabetes model induced by streptozotocin (STZ) . All animals underwent partial left carotid artery (PLCA) ligation. The carotid arteries were collected , the number of M1 macrophages was detected by immunohistochemistry , and the level of AGEs was analyzed by ELISA.Microvascular endothelial cell line bEnd. 3 cells were treated with conditioned medium (CM) of AGEs treated RAW264. 7 cells or Exos derived from RAW264. 7 , followed by evaluations of the cell barrier function and mitochondrial function. @*Results @#There was an increased number of M1 macrophages in carotid atherosclerotic tissues of diabetic mice and in AGEs treated RAW264. 7 cells. CM or Exos significantly induced barrier dysfunction , reactive oxygen species (ROS) accumulation and mitochondrial dysfunction in vascular endothelial cells in vitro. In addition , bioinformatics analysis showed that miR⁃92a was up⁃regulated in Exos derived from macrophages stimulated by AGEs. Experimentally , Exos participated in CM⁃induced barrier dysfunction , ROS accumulation and mitochondrial dysfunction in bEnd. 3 cells by transferring miR⁃92a. Finally , a series of rescue experiments further confirmed that Exos regulated the barrier dysfunction and mitochondrial function in vascular endothelial cells through miR⁃92a.@*Conclusion@#The expression of AGEs and the number of M1 macrophages in diabetic ApoE - / - mice increase , and AGEs stimulates Exos from macrophages could impair the barrier function and mitochondrial function in vascular endothelial cells by delivering miR⁃92a in vitro.
Полный текст:
1
База данных:
WPRIM
Язык:
Zh
Журнал:
Acta Universitatis Medicinalis Anhui
Год:
2023
Тип:
Article