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Thesis
In vitro and ex vivo substrate stiffness effects on endothelial monolayer permeability in response to TNF-[alpha]
Master of Science (M.S.), Drexel University
01 May 2015
DOI:
https://doi.org/10.17918/etd-6498
Abstract
Hypertension affects 67 million American adults and is a major risk factor for atherosclerosis. While hypertension was once thought to lead to adaptive vascular stiffening, recent studies suggest that reversible vascular stiffening precedes hypertension development. In addition, increased inflammation, such as elevated inflammatory cytokine tumor necrosis factor-[alpha] (TNF-[alpha]), is associated with hypertension. Both stiff substrates and TNF-[alpha] increase endothelial cell permeability, which contributes to atherosclerotic plaque development; however, the impact of substrate stiffness on endothelial cell permeability with TNF-[alpha] has not previously been investigated. In this project, we developed an assay to measured endothelial cell permeability with TNF-[alpha] on different stiffness polyacrylamide (PA) gels. We also created an ex vivo tissue chamber to enable en face fluorescent imaging of live mouse aortae for real time quantification of endothelial cell permeability in intact vessels exposed to flow. Our data confirms the increase in permeability with TNF-[alpha] treatment and substrate stiffness and suggests an interaction between inflammation and stiffness on endothelial cell permeability. This research enhanced our understanding of the integrated impact of substrate stiffness and inflammatory molecules on endothelial barrier loss. This can lead to a greater understanding of how hypertension contributes to atherosclerosis. By improving our knowledge of the interactions between biomechanical and biochemical stimuli, we can develop targeted hypertension therapies.
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Details
- Title
- In vitro and ex vivo substrate stiffness effects on endothelial monolayer permeability in response to TNF-[alpha]
- Creators
- Christina Maria Furia - DU
- Contributors
- Alisa Morss Clyne (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Master of Science (M.S.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xi, 83 pages
- Resource Type
- Thesis
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems (1997-2026); Drexel University
- Other Identifier
- 6498; 991014631951604721