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Role of NADPH Oxidase-4 in Human Endothelial Progenitor Cells

Introduction: Endothelial progenitor cells (EPCs) display a unique ability to promote angiogenesis and restore endothelial function in injured blood vessels. NADPH oxidase 4 (NOX4)-derived hydrogen peroxide (H(2)O(2)) serves as a signaling molecule and promotes endothelial cell proliferation and mig...

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Autores principales: Hakami, Nora Y., Ranjan, Amaresh K., Hardikar, Anandwardhan A., Dusting, Greg J., Peshavariya, Hitesh M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5362645/
https://www.ncbi.nlm.nih.gov/pubmed/28386230
http://dx.doi.org/10.3389/fphys.2017.00150
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author Hakami, Nora Y.
Ranjan, Amaresh K.
Hardikar, Anandwardhan A.
Dusting, Greg J.
Peshavariya, Hitesh M.
author_facet Hakami, Nora Y.
Ranjan, Amaresh K.
Hardikar, Anandwardhan A.
Dusting, Greg J.
Peshavariya, Hitesh M.
author_sort Hakami, Nora Y.
collection PubMed
description Introduction: Endothelial progenitor cells (EPCs) display a unique ability to promote angiogenesis and restore endothelial function in injured blood vessels. NADPH oxidase 4 (NOX4)-derived hydrogen peroxide (H(2)O(2)) serves as a signaling molecule and promotes endothelial cell proliferation and migration as well as protecting against cell death. However, the role of NOX4 in EPC function is not completely understood. Methods: EPCs were isolated from human saphenous vein and mammary artery discarded during bypass surgery. NOX4 gene and protein expression in EPCs were measured by real time-PCR and Western blot analysis respectively. NOX4 gene expression was inhibited using an adenoviral vector expressing human NOX4 shRNA (Ad-NOX4i). H(2)O(2) production was measured by Amplex red assay. EPC migration was evaluated using a transwell migration assay. EPC proliferation and viability were measured using trypan blue counts. Results: Inhibition of NOX4 using Ad-NOX4i reduced Nox4 gene and protein expression as well as H(2)O(2) formation in EPCs. Inhibition of NOX4-derived H(2)O(2) decreased both proliferation and migration of EPCs. Interestingly, pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) decreased NOX4 expression and reduced survival of EPCs. However, the survival of EPCs was further diminished by TNF-α in NOX4-knockdown cells, suggesting that NOX4 has a protective role in EPCs. Conclusion: These findings suggest that NOX4-type NADPH oxidase is important for proliferation and migration functions of EPCs and protects against pro-inflammatory cytokine induced EPC death. These properties of NOX4 may facilitate the efficient function of EPCs which is vital for successful neovascularization.
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spelling pubmed-53626452017-04-06 Role of NADPH Oxidase-4 in Human Endothelial Progenitor Cells Hakami, Nora Y. Ranjan, Amaresh K. Hardikar, Anandwardhan A. Dusting, Greg J. Peshavariya, Hitesh M. Front Physiol Physiology Introduction: Endothelial progenitor cells (EPCs) display a unique ability to promote angiogenesis and restore endothelial function in injured blood vessels. NADPH oxidase 4 (NOX4)-derived hydrogen peroxide (H(2)O(2)) serves as a signaling molecule and promotes endothelial cell proliferation and migration as well as protecting against cell death. However, the role of NOX4 in EPC function is not completely understood. Methods: EPCs were isolated from human saphenous vein and mammary artery discarded during bypass surgery. NOX4 gene and protein expression in EPCs were measured by real time-PCR and Western blot analysis respectively. NOX4 gene expression was inhibited using an adenoviral vector expressing human NOX4 shRNA (Ad-NOX4i). H(2)O(2) production was measured by Amplex red assay. EPC migration was evaluated using a transwell migration assay. EPC proliferation and viability were measured using trypan blue counts. Results: Inhibition of NOX4 using Ad-NOX4i reduced Nox4 gene and protein expression as well as H(2)O(2) formation in EPCs. Inhibition of NOX4-derived H(2)O(2) decreased both proliferation and migration of EPCs. Interestingly, pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) decreased NOX4 expression and reduced survival of EPCs. However, the survival of EPCs was further diminished by TNF-α in NOX4-knockdown cells, suggesting that NOX4 has a protective role in EPCs. Conclusion: These findings suggest that NOX4-type NADPH oxidase is important for proliferation and migration functions of EPCs and protects against pro-inflammatory cytokine induced EPC death. These properties of NOX4 may facilitate the efficient function of EPCs which is vital for successful neovascularization. Frontiers Media S.A. 2017-03-23 /pmc/articles/PMC5362645/ /pubmed/28386230 http://dx.doi.org/10.3389/fphys.2017.00150 Text en Copyright © 2017 Hakami, Ranjan, Hardikar, Dusting and Peshavariya. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Hakami, Nora Y.
Ranjan, Amaresh K.
Hardikar, Anandwardhan A.
Dusting, Greg J.
Peshavariya, Hitesh M.
Role of NADPH Oxidase-4 in Human Endothelial Progenitor Cells
title Role of NADPH Oxidase-4 in Human Endothelial Progenitor Cells
title_full Role of NADPH Oxidase-4 in Human Endothelial Progenitor Cells
title_fullStr Role of NADPH Oxidase-4 in Human Endothelial Progenitor Cells
title_full_unstemmed Role of NADPH Oxidase-4 in Human Endothelial Progenitor Cells
title_short Role of NADPH Oxidase-4 in Human Endothelial Progenitor Cells
title_sort role of nadph oxidase-4 in human endothelial progenitor cells
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5362645/
https://www.ncbi.nlm.nih.gov/pubmed/28386230
http://dx.doi.org/10.3389/fphys.2017.00150
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