Geck powerup5/25/2023 These results provide key insights into the metabolic alterations that occur in endothelial cells in response to hypoxia, which serve as a foundation for future studies to develop therapies that lead to vessel normalization and more efficient drug delivery.Ĭitation: Cohen EB, Geck RC, Toker A (2020) Metabolic pathway alterations in microvascular endothelial cells in response to hypoxia. Additionally, there were significant changes in de novo pyrimidine synthesis as well as glutathione and taurine metabolism. We found that many amino acid-related metabolites were altered by hypoxia exposure, especially within alanine-aspartate-glutamate, serine-threonine, and cysteine-methionine metabolism. 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. ![]() However, the metabolic alterations of endothelial cells in response to hypoxia have been relatively unexplored. Recent studies have explored the efficacy of targeting metabolic pathways in tumor cells in combination with anti-angiogenic therapy. Therefore, most anti-angiogenic therapies are generally inefficient and result in acquired resistance to increased hypoxia due to elimination of the vasculature. ![]() ![]() Endothelial cells that comprise the vasculature are poorly connected causing vessel leakage and exposing the endothelium to a hypoxic microenvironment. The vasculature within a tumor is highly disordered both structurally and functionally.
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