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Arterial Levels of Oxygen Stimulate Intimal Hyperplasia in Human Saphenous Veins via a ROS-Dependent Mechanism

Saphenous veins used as arterial grafts are exposed to arterial levels of oxygen partial pressure (pO(2)), which are much greater than what they experience in their native environment. The object of this study is to determine the impact of exposing human saphenous veins to arterial pO(2). Saphenous...

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Autores principales: Joddar, Binata, Firstenberg, Michael S., Reen, Rashmeet K., Varadharaj, Saradhadevi, Khan, Mahmood, Childers, Rachel C., Zweier, Jay L., Gooch, Keith J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4370681/
https://www.ncbi.nlm.nih.gov/pubmed/25799140
http://dx.doi.org/10.1371/journal.pone.0120301
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author Joddar, Binata
Firstenberg, Michael S.
Reen, Rashmeet K.
Varadharaj, Saradhadevi
Khan, Mahmood
Childers, Rachel C.
Zweier, Jay L.
Gooch, Keith J.
author_facet Joddar, Binata
Firstenberg, Michael S.
Reen, Rashmeet K.
Varadharaj, Saradhadevi
Khan, Mahmood
Childers, Rachel C.
Zweier, Jay L.
Gooch, Keith J.
author_sort Joddar, Binata
collection PubMed
description Saphenous veins used as arterial grafts are exposed to arterial levels of oxygen partial pressure (pO(2)), which are much greater than what they experience in their native environment. The object of this study is to determine the impact of exposing human saphenous veins to arterial pO(2). Saphenous veins and left internal mammary arteries from consenting patients undergoing coronary artery bypass grafting were cultured ex vivo for 2 weeks in the presence of arterial or venous pO(2) using an established organ culture model. Saphenous veins cultured with arterial pO(2) developed intimal hyperplasia as evidenced by 2.8-fold greater intimal area and 5.8-fold increase in cell proliferation compared to those freshly isolated. Saphenous veins cultured at venous pO(2) or internal mammary arteries cultured at arterial pO(2) did not develop intimal hyperplasia. Intimal hyperplasia was accompanied by two markers of elevated reactive oxygen species (ROS): increased dihydroethidium associated fluorescence (4-fold, p<0.05) and increased levels of the lipid peroxidation product, 4-hydroxynonenal (10-fold, p<0.05). A functional role of the increased ROS saphenous veins exposed to arterial pO(2) is suggested by the observation that chronic exposure to tiron, a ROS scavenger, during the two-week culture period, blocked intimal hyperplasia. Electron paramagnetic resonance based oximetry revealed that the pO(2) in the wall of the vessel tracked that of the atmosphere with a ~30 mmHg offset, thus the cells in the vessel wall were directly exposed to variations in pO(2). Monolayer cultures of smooth muscle cells isolated from saphenous veins exhibited increased proliferation when exposed to arterial pO(2) relative to those cultured at venous pO(2). This increased proliferation was blocked by tiron. Taken together, these data suggest that exposure of human SV to arterial pO(2) stimulates IH via a ROS-dependent pathway.
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spelling pubmed-43706812015-04-04 Arterial Levels of Oxygen Stimulate Intimal Hyperplasia in Human Saphenous Veins via a ROS-Dependent Mechanism Joddar, Binata Firstenberg, Michael S. Reen, Rashmeet K. Varadharaj, Saradhadevi Khan, Mahmood Childers, Rachel C. Zweier, Jay L. Gooch, Keith J. PLoS One Research Article Saphenous veins used as arterial grafts are exposed to arterial levels of oxygen partial pressure (pO(2)), which are much greater than what they experience in their native environment. The object of this study is to determine the impact of exposing human saphenous veins to arterial pO(2). Saphenous veins and left internal mammary arteries from consenting patients undergoing coronary artery bypass grafting were cultured ex vivo for 2 weeks in the presence of arterial or venous pO(2) using an established organ culture model. Saphenous veins cultured with arterial pO(2) developed intimal hyperplasia as evidenced by 2.8-fold greater intimal area and 5.8-fold increase in cell proliferation compared to those freshly isolated. Saphenous veins cultured at venous pO(2) or internal mammary arteries cultured at arterial pO(2) did not develop intimal hyperplasia. Intimal hyperplasia was accompanied by two markers of elevated reactive oxygen species (ROS): increased dihydroethidium associated fluorescence (4-fold, p<0.05) and increased levels of the lipid peroxidation product, 4-hydroxynonenal (10-fold, p<0.05). A functional role of the increased ROS saphenous veins exposed to arterial pO(2) is suggested by the observation that chronic exposure to tiron, a ROS scavenger, during the two-week culture period, blocked intimal hyperplasia. Electron paramagnetic resonance based oximetry revealed that the pO(2) in the wall of the vessel tracked that of the atmosphere with a ~30 mmHg offset, thus the cells in the vessel wall were directly exposed to variations in pO(2). Monolayer cultures of smooth muscle cells isolated from saphenous veins exhibited increased proliferation when exposed to arterial pO(2) relative to those cultured at venous pO(2). This increased proliferation was blocked by tiron. Taken together, these data suggest that exposure of human SV to arterial pO(2) stimulates IH via a ROS-dependent pathway. Public Library of Science 2015-03-23 /pmc/articles/PMC4370681/ /pubmed/25799140 http://dx.doi.org/10.1371/journal.pone.0120301 Text en © 2015 Joddar 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
Joddar, Binata
Firstenberg, Michael S.
Reen, Rashmeet K.
Varadharaj, Saradhadevi
Khan, Mahmood
Childers, Rachel C.
Zweier, Jay L.
Gooch, Keith J.
Arterial Levels of Oxygen Stimulate Intimal Hyperplasia in Human Saphenous Veins via a ROS-Dependent Mechanism
title Arterial Levels of Oxygen Stimulate Intimal Hyperplasia in Human Saphenous Veins via a ROS-Dependent Mechanism
title_full Arterial Levels of Oxygen Stimulate Intimal Hyperplasia in Human Saphenous Veins via a ROS-Dependent Mechanism
title_fullStr Arterial Levels of Oxygen Stimulate Intimal Hyperplasia in Human Saphenous Veins via a ROS-Dependent Mechanism
title_full_unstemmed Arterial Levels of Oxygen Stimulate Intimal Hyperplasia in Human Saphenous Veins via a ROS-Dependent Mechanism
title_short Arterial Levels of Oxygen Stimulate Intimal Hyperplasia in Human Saphenous Veins via a ROS-Dependent Mechanism
title_sort arterial levels of oxygen stimulate intimal hyperplasia in human saphenous veins via a ros-dependent mechanism
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4370681/
https://www.ncbi.nlm.nih.gov/pubmed/25799140
http://dx.doi.org/10.1371/journal.pone.0120301
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