To explore the mechanism of AGEs on diabetic endothelial cell damage based on monocyte⁃macrophage exosomes/microRNA⁃92a
10.19405/j.cnki.issn1000-1492.2023.01.015
- Author:
Yan Li
1
;
Xinju Zhang
1
;
Wu Liu
1
;
Jinfeng Li
1
;
Yan Sun
1
;
Hui Li
2
;
Jieping Cheng
1
Author Information
1. Dept ofEndocrinology,Xinjiang Production and Construction Corps Hospital ( The Second Afiliated Hospital of Shihezi University School ofMedicine) , Urumqi 830092
2. Administrative Organ , Xinjiang Production and Construction Corps Hospital ( The Second Afiliated Hospital of Shihezi University School ofMedicine) , Urumqi 830092
- Publication Type:Journal Article
- Keywords:
macrophages;
exosomes;
microRNA⁃92a;
advanced glycation end products;
diabetes;
endothelial cell damage
- From:
Acta Universitatis Medicinalis Anhui
2023;58(1):85-94
- CountryChina
- Language:Chinese
-
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.
- Full text:2024070716144003270基于单核巨噬细胞外泌体_m...尿病内皮细胞损伤的作用机制_李雁.pdf
