Modeling early stage atherosclerosis in a primary human vascular microphysiological system

Xu Zhang, Muath Bishawi, Ge Zhang, Varun Prasad, Ellen Salmon, Jason J. Breithaupt, Qiao Zhang and George A. Truskey ()
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Xu Zhang: Duke University
Muath Bishawi: Duke University
Ge Zhang: Dalian Medical University
Varun Prasad: Duke University
Ellen Salmon: Duke University
Jason J. Breithaupt: Duke University
Qiao Zhang: Duke University
George A. Truskey: Duke University

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-19197-8

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