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 (pO2), 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 pO2. Saphenous vein...

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Bibliographic Details
Published in:PloS one 2015-03, Vol.10 (3), p.e0120301-e0120301
Main Authors: Joddar, Binata, Firstenberg, Michael S, Reen, Rashmeet K, Varadharaj, Saradhadevi, Khan, Mahmood, Childers, Rachel C, Zweier, Jay L, Gooch, Keith J
Format: Article
Language:English
Subjects:
1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt - pharmacology
4-Hydroxynonenal
Aldehydes - metabolism
Analysis
Arteries
Arteries - metabolism
Atherosclerosis
Biomedical engineering
Cardiac patients
Cardiovascular disease
Cell culture
Cell proliferation
Chronic exposure
Coronary artery
Coronary artery bypass
Electron paramagnetic resonance
Engineering
Exposure
Fluorescence
Free Radical Scavengers - pharmacology
Grafts
Heart
Humans
Hyperoxia
Hyperplasia
Hyperplasia - metabolism
Hypoxia
Kinases
Lipid Peroxidation
Muscles
Organ culture
Oxidative stress
Oximetry
Oxygen
Oxygen - blood
Partial pressure
Peroxidation
Reactive oxygen species
Reactive Oxygen Species - metabolism
Saphenous Vein - metabolism
Saphenous Vein - pathology
Smooth muscle
Surgery
Tunica Intima - drug effects
Tunica Intima - metabolism
Tunica Intima - pathology
Veins
Veins & arteries
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Summary:Saphenous veins used as arterial grafts are exposed to arterial levels of oxygen partial pressure (pO2), 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 pO2. 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 pO2 using an established organ culture model. Saphenous veins cultured with arterial pO2 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 pO2 or internal mammary arteries cultured at arterial pO2 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
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0120301