Application of Oxidative Stress to a Tissue-Engineered Vascular Aging Model Induces Endothelial Cell Senescence and Activation.

Journal Article (Journal Article)

Clinical studies have established a connection between oxidative stress, aging, and atherogenesis. These factors contribute to senescence and inflammation in the endothelium and significant reductions in endothelium-dependent vasoreactivity in aged patients. Tissue-engineered blood vessels (TEBVs) recapitulate the structure and function of arteries and arterioles in vitro. We developed a TEBV model for vascular senescence and examined the relative influence of endothelial cell and smooth muscle cell senescence on vasoreactivity. Senescence was induced in 2D endothelial cell cultures and TEBVs by exposure to 100 µM H2 O2 for one week to model chronic oxidative stress. H2 O2 treatment significantly increased senescence in endothelial cells and mural cells, human neonatal dermal fibroblasts (hNDFs), as measured by increased p21 levels and reduced NOS3 expression. Although H2 O2 treatment induced senescence in both the endothelial cells (ECs) and hNDFs, the functional effects on the vasculature were endothelium specific. Expression of the leukocyte adhesion molecule vascular cell adhesion molecule 1 (VCAM-1) was increased in the ECs, and endothelium-dependent vasodilation decreased. Vasoconstriction and endothelium-independent vasodilation were preserved despite mural cell senescence. The results suggest that the functional effects of vascular cell senescence are dominated by the endothelium.

Full Text

Duke Authors

Cited Authors

  • Salmon, EE; Breithaupt, JJ; Truskey, GA

Published Date

  • May 22, 2020

Published In

Volume / Issue

  • 9 / 5

PubMed ID

  • 32455928

Pubmed Central ID

  • PMC7290800

Electronic International Standard Serial Number (EISSN)

  • 2073-4409

International Standard Serial Number (ISSN)

  • 2073-4409

Digital Object Identifier (DOI)

  • 10.3390/cells9051292

Language

  • eng