DOI: 10.1002/ame2.12324
Overexpression of ACE2 ameliorates Aβ-induced blood-brain barrier damage and angiogenesis by inhibiting NF-κB/VEGF/VEGFR2 pathway
Xueling Zhang1
Yu Zhang2
Ling Zhang2
Chuan Qin2
1.institute of Laboratory Animal Sciences,CAMS & PUMC,Beijing,China2.institute of Laboratory Animal Sciences,CAMS & PUMC,Beijing,China;National Human Diseases Animal Model Resource Center,Beijing,China;NHC Key Laboratory of Human Disease Comparative Medicine,Beijing,China;Changping National Laboratory(CPNL),Beijing,China
摘要：Background:Pathological angiogenesis and blood-brain barrier damage may play an important role in Alzheimer's disease(AD).ACE2 is mainly expressed on the surface of endothelial cells in brain.Recent studies have shown that the expression of ACE2 in AD is reduced,but its role in AD is still unclear.Method:We induced AD damage in endothelial cells using Aβ25-35 and overex-pressed ACE2 in bEend.3 cells through lentiviral transfection.We detected the ef-fect of Aβ25-35 on cell viability using the CCK-8 assay and examined the effect of overexpressing ACE2 on angiogenesis using an angiogenesis assay.We used western blot and cell immunofluorescence to detect changes in the expression of the VEGF/VEGFR2 pathway,tight junction protein,and NF-κB pathway.Results:Aβ25-35 treatment significantly decreased the expression of ACE2 and re-duced cell viability.ACE2 overexpression(1)reduced the number of branches and junctions in tube formation,(2)inhibited the activation of the VEGF/VEGFR2 pathway induced by Aβ25-35,(3)increased the expression of TJPs,including ZO-1 and claudin-5,and(4)restored Aβ25-35-induced activation of the NF-κB pathway.Conclusion:Overexpression of ACE2 can improve pathological angiogenesis and blood-brain barrier damage in AD models in vitro by inhibiting NF-κB/VEGF/VEGFR2 pathway activity.ACE2 may therefore represent a therapeutic target for endothelial cell dysfunction in AD.
机标关键词：
论文发表日期：2023-06-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：8( 237-244 )
英文信息