Abstract
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 Aβ(25-35) and overexpressed ACE2 in bEend.3 cells through lentiviral transfection. We detected the effect of Aβ(25-35) 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: Aβ(25-35) treatment significantly decreased the expression of ACE2 and reduced 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 Aβ(25-35) , (3) increased the expression of TJPs, including ZO-1 and claudin-5, and (4) restored Aβ(25-35) -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.