Metabolic pathway alterations in microvascular endothelial cells in response to hypoxia.
The vasculature within a tumor is highly disordered both structurally and functionally. Endothelial cells that comprise the vasculature are poorly connected causing vessel leakage and exposing the endothelium to a hypoxic microenvironment. Therefore, most anti-angiogenic therapies are generally inef...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2020-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0232072&type=printable |
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| author | Emily B Cohen Renee C Geck Alex Toker |
| author_facet | Emily B Cohen Renee C Geck Alex Toker |
| author_sort | Emily B Cohen |
| collection | DOAJ |
| description | The vasculature within a tumor is highly disordered both structurally and functionally. Endothelial cells that comprise the vasculature are poorly connected causing vessel leakage 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 have 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. We found that 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 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. |
| format | Article |
| id | doaj-art-28cef05febf0425997ec867350d5fbff |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-28cef05febf0425997ec867350d5fbff2025-08-20T02:00:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01157e023207210.1371/journal.pone.0232072Metabolic pathway alterations in microvascular endothelial cells in response to hypoxia.Emily B CohenRenee C GeckAlex TokerThe vasculature within a tumor is highly disordered both structurally and functionally. Endothelial cells that comprise the vasculature are poorly connected causing vessel leakage 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 have 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. We found that 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 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0232072&type=printable |
| spellingShingle | Emily B Cohen Renee C Geck Alex Toker Metabolic pathway alterations in microvascular endothelial cells in response to hypoxia. PLoS ONE |
| title | Metabolic pathway alterations in microvascular endothelial cells in response to hypoxia. |
| title_full | Metabolic pathway alterations in microvascular endothelial cells in response to hypoxia. |
| title_fullStr | Metabolic pathway alterations in microvascular endothelial cells in response to hypoxia. |
| title_full_unstemmed | Metabolic pathway alterations in microvascular endothelial cells in response to hypoxia. |
| title_short | Metabolic pathway alterations in microvascular endothelial cells in response to hypoxia. |
| title_sort | metabolic pathway alterations in microvascular endothelial cells in response to hypoxia |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0232072&type=printable |
| work_keys_str_mv | AT emilybcohen metabolicpathwayalterationsinmicrovascularendothelialcellsinresponsetohypoxia AT reneecgeck metabolicpathwayalterationsinmicrovascularendothelialcellsinresponsetohypoxia AT alextoker metabolicpathwayalterationsinmicrovascularendothelialcellsinresponsetohypoxia |