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Endothelium Derived Nitric Oxide Synthase Negatively Regulates the PDGF-Survivin Pathway during Flow-Dependent Vascular Remodeling
Chronic alterations in blood flow initiate structural changes in vessel lumen caliber to normalize shear stress. The loss of endothelial derived nitric oxide synthase (eNOS) in mice promotes abnormal flow dependent vascular remodeling, thus uncoupling mechanotransduction from adaptive vascular remod...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3280303/ https://www.ncbi.nlm.nih.gov/pubmed/22355372 http://dx.doi.org/10.1371/journal.pone.0031495 |
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author | Yu, Jun Zhang, Yuanyuan Zhang, Xinbo Rudic, R. Daniel Bauer, Philip M. Altieri, Dario C. Sessa, William C. |
author_facet | Yu, Jun Zhang, Yuanyuan Zhang, Xinbo Rudic, R. Daniel Bauer, Philip M. Altieri, Dario C. Sessa, William C. |
author_sort | Yu, Jun |
collection | PubMed |
description | Chronic alterations in blood flow initiate structural changes in vessel lumen caliber to normalize shear stress. The loss of endothelial derived nitric oxide synthase (eNOS) in mice promotes abnormal flow dependent vascular remodeling, thus uncoupling mechanotransduction from adaptive vascular remodeling. However, the mechanisms of how the loss of eNOS promotes abnormal remodeling are not known. Here we show that abnormal flow-dependent remodeling in eNOS knockout mice (eNOS (−/−)) is associated with activation of the platelet derived growth factor (PDGF) signaling pathway leading to the induction of the inhibitor of apoptosis, survivin. Interfering with PDGF signaling or survivin function corrects the abnormal remodeling seen in eNOS (−/−) mice. Moreover, nitric oxide (NO) negatively regulates PDGF driven survivin expression and cellular proliferation in cultured vascular smooth muscle cells. Collectively, our data suggests that eNOS negatively regulates the PDGF-survivin axis to maintain proportional flow-dependent luminal remodeling and vascular quiescence. |
format | Online Article Text |
id | pubmed-3280303 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-32803032012-02-21 Endothelium Derived Nitric Oxide Synthase Negatively Regulates the PDGF-Survivin Pathway during Flow-Dependent Vascular Remodeling Yu, Jun Zhang, Yuanyuan Zhang, Xinbo Rudic, R. Daniel Bauer, Philip M. Altieri, Dario C. Sessa, William C. PLoS One Research Article Chronic alterations in blood flow initiate structural changes in vessel lumen caliber to normalize shear stress. The loss of endothelial derived nitric oxide synthase (eNOS) in mice promotes abnormal flow dependent vascular remodeling, thus uncoupling mechanotransduction from adaptive vascular remodeling. However, the mechanisms of how the loss of eNOS promotes abnormal remodeling are not known. Here we show that abnormal flow-dependent remodeling in eNOS knockout mice (eNOS (−/−)) is associated with activation of the platelet derived growth factor (PDGF) signaling pathway leading to the induction of the inhibitor of apoptosis, survivin. Interfering with PDGF signaling or survivin function corrects the abnormal remodeling seen in eNOS (−/−) mice. Moreover, nitric oxide (NO) negatively regulates PDGF driven survivin expression and cellular proliferation in cultured vascular smooth muscle cells. Collectively, our data suggests that eNOS negatively regulates the PDGF-survivin axis to maintain proportional flow-dependent luminal remodeling and vascular quiescence. Public Library of Science 2012-02-15 /pmc/articles/PMC3280303/ /pubmed/22355372 http://dx.doi.org/10.1371/journal.pone.0031495 Text en Yu et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Yu, Jun Zhang, Yuanyuan Zhang, Xinbo Rudic, R. Daniel Bauer, Philip M. Altieri, Dario C. Sessa, William C. Endothelium Derived Nitric Oxide Synthase Negatively Regulates the PDGF-Survivin Pathway during Flow-Dependent Vascular Remodeling |
title | Endothelium Derived Nitric Oxide Synthase Negatively Regulates the PDGF-Survivin Pathway during Flow-Dependent Vascular Remodeling |
title_full | Endothelium Derived Nitric Oxide Synthase Negatively Regulates the PDGF-Survivin Pathway during Flow-Dependent Vascular Remodeling |
title_fullStr | Endothelium Derived Nitric Oxide Synthase Negatively Regulates the PDGF-Survivin Pathway during Flow-Dependent Vascular Remodeling |
title_full_unstemmed | Endothelium Derived Nitric Oxide Synthase Negatively Regulates the PDGF-Survivin Pathway during Flow-Dependent Vascular Remodeling |
title_short | Endothelium Derived Nitric Oxide Synthase Negatively Regulates the PDGF-Survivin Pathway during Flow-Dependent Vascular Remodeling |
title_sort | endothelium derived nitric oxide synthase negatively regulates the pdgf-survivin pathway during flow-dependent vascular remodeling |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3280303/ https://www.ncbi.nlm.nih.gov/pubmed/22355372 http://dx.doi.org/10.1371/journal.pone.0031495 |
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