AI Article Synopsis

  • - The study introduces a new in vitro model for early atherosclerosis using tissue-engineered blood vessels (TEBVs) that can mimic the conditions of human arteries, demonstrating their durability and function for at least 4 weeks.
  • - When exposed to modified low-density lipoprotein (eLDL) and TNFα, the TEBVs showed increased monocyte accumulation and changes in nitric oxide production, leading to significant cellular alterations associated with atherosclerosis.
  • - The model can help evaluate the impact of drugs, such as lovastatin, on vascular functions, revealing that certain treatments can reduce harmful cell interactions and foam cell formation, which is crucial for understanding atherosclerosis therapeutics.

Article 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 P2Y 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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591486PMC
http://dx.doi.org/10.1038/s41467-020-19197-8DOI Listing

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