{
  "abstract": "The Beta Site Amyloid Precursor Protein Cleavage Enzyme 1 (BACE1) contributes to Alzheimer’s disease through the processing of neurotoxic Aβ peptides. BACE1 has additionally been associated with cardiovascular disease incidence and prognosis, with Aβ deposits recently being discovered in human atherosclerotic plaquesTo investigate the role of BACE1 in atherosclerosis development, we utilized the Apoe−/− mouse model. Treatment with the BACE1 inhibitor M3 resulted in a 50% reduction in atherosclerotic lesion area compared to age-matched controls, as assessed by Oil Red O staining of both the aortic arch and whole aorta. In atherosclerosis, endothelial mesenchymal transition (EndMT) is increasingly observed, wherein endothelial cells lose their typical properties and acquire a pro-inflammatory, pro-fibrotic phenotype. To explore this mechanism, we induced EndMT in human umbilical vein endothelial cells (HUVECs) in vitro using TGF-β2 and IL-1β. EndMT cells exhibited striking morphological changes, an increase in mesenchymal protein expression (α-SMA, Sm22α) and a concurrent decrease in endothelial-specific markers (VE-Cadherin, CD31, eNOS). Notably, BACE1 protein expression increased two-fold, suggesting a potential role in EndMT regulation. Further supporting this, BACE1 overexpression potentiated mesenchymal-like morphological changes during EndMT, while BACE1 inhibition suppressed the expression of the EndMT-associated transcription factor SNAI1 following TGF-β2 and IL-1β exposure.Taken together, these findings suggest that BACE1 modulates atherosclerosis potentially through EndMT and highlights BACE1 as a novel therapeutic target for atherosclerotic cardiovascular disease.",
  "authors": [
    {
      "affiliations": [
        "University of Leeds, Leeds, UK"
      ],
      "name": "Maximilian Lester"
    },
    {
      "affiliations": [
        "University of Leeds, Leeds, UK"
      ],
      "name": "Lia Pinto"
    },
    {
      "affiliations": [
        "University of Leeds, Leeds, UK"
      ],
      "name": "Paul Meakin"
    }
  ],
  "title": "BS27 BACE1 modulates atherosclerosis through endothelial dysfunction",
  "uid": "905a79f0-9a9d-5ce4-bcdb-c7ddb7632258"
}