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- W3133372010 abstract "β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) is a transmembrane aspartylprotease notorious for its contribution to the aetiology of Alzheimer’s disease (AD). Notably, BACE1is elevated in diseases displaying aberrant angiogenesis, including diabetes mellitus (DM), and isimplicated in VEGF Receptor 1 (VEGFR1) proteolysis (Devi et al., 2012 and Cai et al., 2012).Therefore, we hypothesise that increased BACE1 activity in DM contributes to the alteredangiogenesis displayed in associated microvascular complications, including diabetic foot ulcers(DFUs), and that BACE1 inhibitors may prevent such problems.In vivo observations of the endothelium in the retina of BACE1-/- mice displayed a hyper-branchingphenotype in comparison to wild types. This was characterised by a decrease in radial outgrowth butan increase in branch points, percentage vasculature area and quantity of filopodia. This finding wasfurther supported in vitro when exploiting the fibrin gel angiogenesis assay. Here, BACE1 inhibitionof human umbilical vein endothelial cells (HUVECs) exhibited an increase in sprouting (17 ± 3%,P=<0.001) compared to controls. Lastly, an increase in the phosphorylation of eNOS at Serine 1177 inHUVECs (+ 0.8 ± 0.2, P=0.05) and primary lung endothelial cells (PECs) (+ 0.2 ± 0.02), prior to VEGFstimulations, provided a possible insight into the pro-angiogenic mechanisms of BACE1 inhibition.Overall, our findings suggest that BACE1 inhibitors, previously trialled to treat AD, could berepurposed to normalise angiogenesis in DM. This may reduce the risk of microvascularcomplications from developing and prevent consequent amputations." @default.
- W3133372010 created "2021-03-01" @default.
- W3133372010 creator A5090058883 @default.
- W3133372010 date "2020-08-01" @default.
- W3133372010 modified "2023-09-26" @default.
- W3133372010 title "Investigating the role of BACE1 in angiogenesis" @default.
- W3133372010 hasPublicationYear "2020" @default.
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