Apr 8, 2020

Metabolic pathway alterations in microvascular endothelial cells in response to hypoxia

BioRxiv : the Preprint Server for Biology
Emily Barbara CohenA. Toker

Abstract

The vasculature within a tumor is highly disordered both structurally and functionally. Endothelial cells that comprise the vasculature are poorly connected causing vessels to be leaky and exposing the endothelium to a hypoxic microenvironment. Therefore, most anti-angiogenic therapies are generally inefficient and result in acquired resistance to increased hypoxia due to elimination of the vasculature. Recent studies have explored the efficacy of targeting metabolic pathways in tumor cells in combination with anti-angiogenic therapy. However, the metabolic alterations of endothelial cells in response to hypoxia has been relatively unexplored. Here, we measured polar metabolite levels in microvascular endothelial cells exposed to short- and long-term hypoxia with the goal of identifying metabolic vulnerabilities that can be targeted to normalize tumor vasculature and improve drug delivery. Many amino acid-related metabolites were altered by hypoxia exposure, especially within alanine-aspartate-glutamate, serine-threonine, and cysteine-methionine metabolism. Additionally, there were significant changes in de novo pyrimidine synthesis as well as glutathione and taurine metabolism. These results provide key insights into the metab...Continue Reading

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Mentioned in this Paper

Genetic Drift
Spatial Memory
Patterns
Isolation Aspects
Spatial Distribution
Environment
Zebrafish
Resistance Process
Gobio
Structure

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