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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...

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Detalles Bibliográficos
Autores principales: Yu, Jun, Zhang, Yuanyuan, Zhang, Xinbo, Rudic, R. Daniel, Bauer, Philip M., Altieri, Dario C., Sessa, William C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
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.
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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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