DOI
https://doi.org/10.25772/4TE3-8H75
Author ORCID Identifier
https://orcid.org/0000-0003-2903-9921
Defense Date
2020
Document Type
Thesis
Degree Name
Master of Science
Department
Biochemistry
First Advisor
Dr. Sarah Spiegel
Abstract
Endothelial cells play an important role in maintaining homeostasis, and disruption of the endothelial barrier have been linked to a number of different pathologies, including cancer metastasis. The vascular endothelial barrier is known to be regulated by a variety of factors, including sphingosine-1-phosphate (S1P), a bioactive lipid metabolite, which has been shown to improve barrier function. However, most studies to date have been focused on the vascular endothelium, and the regulation of the lymphatic endothelial barrier has not been thoroughly investigated. We found that prior to any stimulation the lymphatic endothelial cells (LECs) had a lower trans-endothelial resistance (TER) in comparison to vascular endothelial cells (VECs). LECs were more sensitive to stimulation with S1P, asthey displayed a maximal increase in TER with 500 nM S1P, in comparison to VECs which showed a maximal increase in TER with 1 μM S1P. Additionally, the disruption of the endothelial barrier by thrombin, lipopolysaccharide (LPS), and co-culture with cancer cells occurred more rapidly for LECs than for VECs. These results indicate that the vascular and lymphatic endothelial barriers are distinct and stimulation with a variety of agonists results in differential effects.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
5-14-2020