Analysis of VEGF--a regulated gene expression in endothelial cells to identify genes linked to angiogenesis.
Angiogenesis is important for many physiological processes, diseases, and also regenerative medicine. Therapies that inhibit the vascular endothelial growth factor (VEGF) pathway have been used in the clinic for cancer and macular degeneration. In cancer applications, these treatments suffer from a...
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doaj-bb3d730f2cbf4ad4ae340513a9e783272020-11-24T22:00:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0169e2488710.1371/journal.pone.0024887Analysis of VEGF--a regulated gene expression in endothelial cells to identify genes linked to angiogenesis.Corban G RiveraSofie MellbergLena Claesson-WelshJoel S BaderAleksander S PopelAngiogenesis is important for many physiological processes, diseases, and also regenerative medicine. Therapies that inhibit the vascular endothelial growth factor (VEGF) pathway have been used in the clinic for cancer and macular degeneration. In cancer applications, these treatments suffer from a "tumor escape phenomenon" where alternative pathways are upregulated and angiogenesis continues. The redundancy of angiogenesis regulation indicates the need for additional studies and new drug targets. We aimed to (i) identify novel and missing angiogenesis annotations and (ii) verify their significance to angiogenesis. To achieve these goals, we integrated the human interactome with known angiogenesis-annotated proteins to identify a set of 202 angiogenesis-associated proteins. Across endothelial cell lines, we found that a significant fraction of these proteins had highly perturbed gene expression during angiogenesis. After treatment with VEGF-A, we found increasing expression of HIF-1α, APP, HIV-1 tat interactive protein 2, and MEF2C, while endoglin, liprin β1 and HIF-2α had decreasing expression across three endothelial cell lines. The analysis showed differential regulation of HIF-1α and HIF-2α. The data also provided additional evidence for the role of endothelial cells in Alzheimer's disease.http://europepmc.org/articles/PMC3172305?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Corban G Rivera Sofie Mellberg Lena Claesson-Welsh Joel S Bader Aleksander S Popel |
spellingShingle |
Corban G Rivera Sofie Mellberg Lena Claesson-Welsh Joel S Bader Aleksander S Popel Analysis of VEGF--a regulated gene expression in endothelial cells to identify genes linked to angiogenesis. PLoS ONE |
author_facet |
Corban G Rivera Sofie Mellberg Lena Claesson-Welsh Joel S Bader Aleksander S Popel |
author_sort |
Corban G Rivera |
title |
Analysis of VEGF--a regulated gene expression in endothelial cells to identify genes linked to angiogenesis. |
title_short |
Analysis of VEGF--a regulated gene expression in endothelial cells to identify genes linked to angiogenesis. |
title_full |
Analysis of VEGF--a regulated gene expression in endothelial cells to identify genes linked to angiogenesis. |
title_fullStr |
Analysis of VEGF--a regulated gene expression in endothelial cells to identify genes linked to angiogenesis. |
title_full_unstemmed |
Analysis of VEGF--a regulated gene expression in endothelial cells to identify genes linked to angiogenesis. |
title_sort |
analysis of vegf--a regulated gene expression in endothelial cells to identify genes linked to angiogenesis. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2011-01-01 |
description |
Angiogenesis is important for many physiological processes, diseases, and also regenerative medicine. Therapies that inhibit the vascular endothelial growth factor (VEGF) pathway have been used in the clinic for cancer and macular degeneration. In cancer applications, these treatments suffer from a "tumor escape phenomenon" where alternative pathways are upregulated and angiogenesis continues. The redundancy of angiogenesis regulation indicates the need for additional studies and new drug targets. We aimed to (i) identify novel and missing angiogenesis annotations and (ii) verify their significance to angiogenesis. To achieve these goals, we integrated the human interactome with known angiogenesis-annotated proteins to identify a set of 202 angiogenesis-associated proteins. Across endothelial cell lines, we found that a significant fraction of these proteins had highly perturbed gene expression during angiogenesis. After treatment with VEGF-A, we found increasing expression of HIF-1α, APP, HIV-1 tat interactive protein 2, and MEF2C, while endoglin, liprin β1 and HIF-2α had decreasing expression across three endothelial cell lines. The analysis showed differential regulation of HIF-1α and HIF-2α. The data also provided additional evidence for the role of endothelial cells in Alzheimer's disease. |
url |
http://europepmc.org/articles/PMC3172305?pdf=render |
work_keys_str_mv |
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