Engineered endothelium model enables recapitulation of vascular function and early atherosclerosis development.

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  • Additional Information
    • Source:
      Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 8100316 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-5905 (Electronic) Linking ISSN: 01429612 NLM ISO Abbreviation: Biomaterials Subsets: MEDLINE
    • Publication Information:
      Publication: <1995-> : Amsterdam : Elsevier Science
      Original Publication: [Guilford, England] : IPC Science and Technology Press, 1980-
    • Subject Terms:
      Atherosclerosis*/pathology ; Atherosclerosis*/metabolism ; Tissue Engineering*/methods ; Endothelium, Vascular*/metabolism ; Cell Adhesion*; Humans ; Basement Membrane/metabolism ; Nitric Oxide/metabolism ; Human Umbilical Vein Endothelial Cells/metabolism ; Pericytes/metabolism ; Pericytes/cytology ; Endothelial Cells/metabolism ; Endothelial Cells/cytology ; Monocytes/metabolism ; Monocytes/cytology ; Adherens Junctions/metabolism ; Extracellular Matrix/metabolism ; Lipoproteins, LDL/metabolism ; Hydrogels/chemistry
    • Abstract:
      Human health relies heavily on the vascular endothelium. Here, we propose a novel engineered endothelium model (EEM), which recapitulated both normal vascular function and pathology. An artificial basement membrane (aBM), where porous polyvinyl alcohol hydrogel was securely integrated with human fibroblast-derived, decellularized extracellular matrix on both sides was fabricated first and followed by endothelial cells (ECs) and pericytes (PCs) adhesion, respectively. Our EEM formed robust adherens junction (VE-cad) and built an impermeable barrier with time, along with the nitric oxide (NO) secretion. In our EEM, ECs and PCs interacted each other via aBM and led to hemoglobin alpha 1 (Hb-α1) development, which was involved in NO control and was strongly interconnected with VE-cad as well. A resilient property of EEM under inflammatory milieu was also confirmed by VE-cad and barrier recovery with time. In particular interest, foam cells formation, a hallmark of atherosclerotic initiation was successfully recapitulated in our EEM, where a series of sequential events were confirmed: human monocytes adhesion, transendothelial migration, and oxidized low-density lipoprotein uptake by macrophages. Collectively, our EEM is excellent in recapitulating not only normal endothelium but early pathologic one, thereby enabling EEM to be a physiologically relevant model for vascular study and disease modeling.
      Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
    • Contributed Indexing:
      Keywords: Endothelial cells; Engineered endothelium model; Foam cells; Hemoglobin-α1; Polyvinyl alcohol
    • Accession Number:
      31C4KY9ESH (Nitric Oxide)
      0 (Lipoproteins, LDL)
      0 (Hydrogels)
    • Publication Date:
      Date Created: 20241018 Date Completed: 20241108 Latest Revision: 20241108
    • Publication Date:
      20241114
    • Accession Number:
      10.1016/j.biomaterials.2024.122889
    • Accession Number:
      39423515