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

TitleModeling early stage atherosclerosis in a primary human vascular microphysiological system.
Publication TypeJournal Article
Year of Publication2020
AuthorsX Zhang, M Bishawi, G Zhang, V Prasad, E Salmon, JJ Breithaupt, Q Zhang, and GA Truskey
JournalNature Communications
Volume11
Issue1
Start Page5426
Date Published10/2020
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.

URLhttps://www.nature.com/articles/s41467-020-19197-8
DOI10.1038/s41467-020-19197-8
Short TitleNature Communications