Extracellular vesicles derived from synovial fluid in patients with rheumatoid arthritis promote angiogenesis of HUVEC
10.13431/j.cnki.immunol.j.20250010
- VernacularTitle:类风湿关节炎滑液来源的细胞外囊泡促进HUVEC血管生成
- Author:
Kaibo WANG
1
;
Chuanhao XU
;
Yanbin TIAN
;
Tai TENG
;
Fengmei TAN
;
Chi ZHANG
;
Hong DENG
;
Yanmeng LI
;
Qin YANG
;
Xinyi WANG
;
Mei HAN
Author Information
1. 750004 银川,宁夏医科大学基础医学院病原生物学与医学免疫学系
- Publication Type:Journal Article
- Keywords:
Rheumatoid arthritis;
Extracellular vesicles;
Angiogenesis;
Synovial fluid;
Human umbilical vein endothelial cells
- From:
Immunological Journal
2025;41(2):72-79
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of extracellular vesicles(EVs)derived from synovial fluid of rheumatoid arthritis(RA)patients on angiogenesis of human umbilical vein endothelial cells,and to preliminarily explore the underlying mechanisms.Methods Synovial fluid samples of knee joint were collected from 20 patients with RA and 20 patients with osteoarthritis(OA)in this study.EVs were purified using ultracentrifugation.The morphology and size of EVs were observed by transmission electron microscopy and nanoparticle tracking analysis.CD9,CD63,cytochrome c(Cyt-c),vascular endothelial growth factor(VEGF),lysyl oxidase(LOX),matrix metalloproteinase 2(MMP2),tumour necrosis factor alpha(TNF-α),transforming growth factor beta1(TGF-β1)in EVs were detected using Western blot.Human umbilical vein endothelial cells(HUVEC)were treated with the EVs.The growth,migration and angiogenesis of HUVEC were observed by CCK8 assay,TranswellTM chamber assay,scratch test and matrigel angiogenesis assay,respectively.The effect of EVs on the PI3K/AKT pathway in HUVEC was assessed using Western blot.Results Both EVs from RA synovial fluid(RA-EVs)and OA synovial fluid(OA-EVs)were cup-shaped,mainly between 30-400 nm in diameter,expressing CD63 and CD9,but not Cyt-c.RA-EVs carried more VEGF,LOX,MMP2,TNF-α and TGF-β1 than OA-EVs.Compared with the OA-EVs intervention,RA-EVs significantly promoted the proliferation,migration,and angiogenesis of HUVECs,as well as upregulated PI3K/AKT phosphorylation.The inhibitor of PI3K suppressed angiogenesis induced by EVs.Conclusion EVs in synovial fluid of RA carried more cytokines and enzymes that related angiogenesis and inflammation.These EVs exert their pro-angiogenic effects by activating the PI3K/AKT pathway,then contributing to the pathological progression of RA.
