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

Publication ,  Journal Article
Salmon, EE; Breithaupt, JJ; Truskey, GA
Published in: Cells
May 2020

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 H2O2 for one week to model chronic oxidative stress. H2O2 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 H2O2 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.

Duke Scholars

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Published In

Cells

DOI

EISSN

2073-4409

ISSN

2073-4409

Publication Date

May 2020

Volume

9

Issue

5

Start / End Page

E1292

Related Subject Headings

  • Vasodilation
  • Vascular Cell Adhesion Molecule-1
  • Tissue Engineering
  • Sirtuin 1
  • Oxidative Stress
  • Models, Biological
  • Inflammation
  • Infant, Newborn
  • Hydrogen Peroxide
  • Humans
 

Citation

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Salmon, E. E., Breithaupt, J. J., & Truskey, G. A. (2020). Application of Oxidative Stress to a Tissue-Engineered Vascular Aging Model Induces Endothelial Cell Senescence and Activation. Cells, 9(5), E1292. https://doi.org/10.3390/cells9051292
Salmon, Ellen E., Jason J. Breithaupt, and George A. Truskey. “Application of Oxidative Stress to a Tissue-Engineered Vascular Aging Model Induces Endothelial Cell Senescence and Activation.Cells 9, no. 5 (May 2020): E1292. https://doi.org/10.3390/cells9051292.
Salmon, Ellen E., et al. “Application of Oxidative Stress to a Tissue-Engineered Vascular Aging Model Induces Endothelial Cell Senescence and Activation.Cells, vol. 9, no. 5, May 2020, p. E1292. Epmc, doi:10.3390/cells9051292.

Published In

Cells

DOI

EISSN

2073-4409

ISSN

2073-4409

Publication Date

May 2020

Volume

9

Issue

5

Start / End Page

E1292

Related Subject Headings

  • Vasodilation
  • Vascular Cell Adhesion Molecule-1
  • Tissue Engineering
  • Sirtuin 1
  • Oxidative Stress
  • Models, Biological
  • Inflammation
  • Infant, Newborn
  • Hydrogen Peroxide
  • Humans