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Modeling early stage atherosclerosis in a primary human vascular microphysiological system.

Publication ,  Journal Article
Zhang, X; Bishawi, M; Zhang, G; Prasad, V; Salmon, E; Breithaupt, JJ; Zhang, Q; Truskey, GA
Published in: Nature communications
October 2020

Novel atherosclerosis models are needed to guide clinical therapy. Here, we report an in vitro model of early atherosclerosis by fabricating and perfusing multi-layer arteriole-scale human tissue-engineered blood vessels (TEBVs) by plastic compression. TEBVs maintain mechanical strength, vasoactivity, and nitric oxide (NO) production for at least 4 weeks. Perfusion of TEBVs at a physiological shear stress with enzyme-modified low-density-lipoprotein (eLDL) with or without TNFα promotes monocyte accumulation, reduces vasoactivity, alters NO production, which leads to endothelial cell activation, monocyte accumulation, foam cell formation and expression of pro-inflammatory cytokines. Removing eLDL leads to recovery of vasoactivity, but not loss of foam cells or recovery of permeability, while pretreatment with lovastatin or the P2Y11 inhibitor NF157 reduces monocyte accumulation and blocks foam cell formation. Perfusion with blood leads to increased monocyte adhesion. This atherosclerosis model can identify the role of drugs on specific vascular functions that cannot be assessed in vivo.

Duke Scholars

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Published In

Nature communications

DOI

EISSN

2041-1723

ISSN

2041-1723

Publication Date

October 2020

Volume

11

Issue

1

Start / End Page

5426

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Tissue Engineering
  • Nitric Oxide
  • Monocytes
  • Models, Biological
  • Lipoproteins, LDL
  • Humans
  • Foam Cells
  • Cells, Cultured
  • Cell Proliferation
 

Citation

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Chicago
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Zhang, X., Bishawi, M., Zhang, G., Prasad, V., Salmon, E., Breithaupt, J. J., … Truskey, G. A. (2020). Modeling early stage atherosclerosis in a primary human vascular microphysiological system. Nature Communications, 11(1), 5426. https://doi.org/10.1038/s41467-020-19197-8
Zhang, Xu, Muath Bishawi, Ge Zhang, Varun Prasad, Ellen Salmon, Jason J. Breithaupt, Qiao Zhang, and George A. Truskey. “Modeling early stage atherosclerosis in a primary human vascular microphysiological system.Nature Communications 11, no. 1 (October 2020): 5426. https://doi.org/10.1038/s41467-020-19197-8.
Zhang X, Bishawi M, Zhang G, Prasad V, Salmon E, Breithaupt JJ, et al. Modeling early stage atherosclerosis in a primary human vascular microphysiological system. Nature communications. 2020 Oct;11(1):5426.
Zhang, Xu, et al. “Modeling early stage atherosclerosis in a primary human vascular microphysiological system.Nature Communications, vol. 11, no. 1, Oct. 2020, p. 5426. Epmc, doi:10.1038/s41467-020-19197-8.
Zhang X, Bishawi M, Zhang G, Prasad V, Salmon E, Breithaupt JJ, Zhang Q, Truskey GA. Modeling early stage atherosclerosis in a primary human vascular microphysiological system. Nature communications. 2020 Oct;11(1):5426.

Published In

Nature communications

DOI

EISSN

2041-1723

ISSN

2041-1723

Publication Date

October 2020

Volume

11

Issue

1

Start / End Page

5426

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Tissue Engineering
  • Nitric Oxide
  • Monocytes
  • Models, Biological
  • Lipoproteins, LDL
  • Humans
  • Foam Cells
  • Cells, Cultured
  • Cell Proliferation