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Title:
Inactivity of nitric oxide synthase gene in the atherosclerotic human carotid artery | Basic Research in Cardiology
Description:
Objective Nitric oxide (NO) inhibits thrombus formation, vascular contraction, and smooth muscle cell proliferation. We investigated whether NO release is enhanced after endothelial NO synthase (eNOS) gene transfer in atherosclerotic human carotid artery ex vivo. Methods and Results Western blotting and immunohistochemistry revealed that transduction enhanced eNOS expression; however, neither nitrite production nor NO release measured by porphyrinic microsensor was altered. In contrast, transduction enhanced NO production in non-atherosclerotic rat aorta and human internal mammary artery. In transduced carotid artery, calcium-dependent eNOS activity was minimal and did not differ from control conditions. Vascular tetrahydrobiopterin concentrations did not differ between the experimental groups.Treatment of transduced carotid artery with FAD, FMN, NADPH, L-arginine, and either sepiapterin or tetrahydrobiopterin did not alter NO release. Superoxide formation was similar in transduced carotid artery and control. Treatment of transduced carotid artery with superoxide dismutase (SOD), PEG-SOD, PEG-catalase did not affect NO release. Conclusions eNOS transduction in atherosclerotic human carotid artery results in high expression without any measurable activity of the recombinant protein. The defect in the atherosclerotic vessels is neither caused by cofactor deficiency nor enhanced NO breakdown. Since angioplasty is performed in atherosclerotic arteries,eNOS gene therapy is unlikely to provide clinical benefit.
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Keywords {🔍}
google, scholar, pubmed, cas, article, nitric, oxide, synthase, gene, artery, human, endothelial, carotid, vascular, nabel, tanner, res, research, phd, transfer, expression, university, switzerland, atherosclerotic, van, cardiovascular, luscher, zürich, basic, lüscher, cell, enos, atherosclerosis, privacy, cookies, content, formation, proliferation, release, disease, hospital, publish, search, loo, shaw, greutert, enhanced, production, transduced, activity,
Topics {✒️}
month download article/chapter adenoviral-mediated gene transfer cyclin-dependent kinase inhibitors apolipoprotein e-deficient mice calcium-dependent enos activity local adenovirus-mediated transfer d'uscio lv nitric oxide isoforms attenuates lesion formation article basic research nitric oxide release transduced carotid artery carotid artery stenting vascular cell proliferation inhibits thrombus formation enos gene therapy human uterine artery human endothelial cells gene transfer approaches van de werf full article pdf van der loo nitric oxide privacy choices/manage cookies bypass graft disease human atherosclerosis adenoviral transfer von segesser lk von zonnefeld aj human forearm vasculature human saphenous vein related subjects integrative human physiology vascular tetrahydrobiopterin concentrations gene therapy tanner fc cardiovascular disease van berkel tjc article tanner european economic area scope submit manuscript genomic elements involved salt-sensitive hypertension direct biochemical evidence gene transfer atherosclerotic rat aorta vascular disease provide clinical benefit high expression rabbit surfactant protein
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mainEntity:
headline:Inactivity of nitric oxide synthase gene in the atherosclerotic human carotid artery
description:Nitric oxide (NO) inhibits thrombus formation, vascular
contraction, and smooth muscle cell proliferation. We investigated
whether NO release is enhanced after endothelial NO synthase (eNOS) gene
transfer in atherosclerotic human carotid artery ex vivo. Western blotting and immunohistochemistry revealed that transduction
enhanced eNOS expression; however, neither nitrite production nor NO
release measured by porphyrinic microsensor was altered. In contrast, transduction
enhanced NO production in non-atherosclerotic rat aorta and human
internal mammary artery. In transduced carotid artery, calcium-dependent
eNOS activity was minimal and did not differ from control
conditions. Vascular tetrahydrobiopterin concentrations did not differ between
the experimental groups.Treatment of transduced carotid artery with
FAD, FMN, NADPH, L-arginine, and either sepiapterin or tetrahydrobiopterin
did not alter NO release. Superoxide formation was similar in
transduced carotid artery and control. Treatment of transduced carotid
artery with superoxide dismutase (SOD), PEG-SOD, PEG-catalase did not affect
NO release. eNOS transduction in atherosclerotic human
carotid artery results in high expression without any measurable activity of
the recombinant protein. The defect in the atherosclerotic vessels is neither
caused by cofactor deficiency nor enhanced NO breakdown. Since angioplasty
is performed in atherosclerotic arteries,eNOS gene therapy is unlikely
to provide clinical benefit.
datePublished:2007-03-15T00:00:00Z
dateModified:2007-03-15T00:00:00Z
pageStart:308
pageEnd:317
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Nitric oxide synthase
gene therapy
adenoviral vector
atherosclerosis
endothelium
Cardiology
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1435-1803
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headline:Inactivity of nitric oxide synthase gene in the atherosclerotic human carotid artery
description:Nitric oxide (NO) inhibits thrombus formation, vascular
contraction, and smooth muscle cell proliferation. We investigated
whether NO release is enhanced after endothelial NO synthase (eNOS) gene
transfer in atherosclerotic human carotid artery ex vivo. Western blotting and immunohistochemistry revealed that transduction
enhanced eNOS expression; however, neither nitrite production nor NO
release measured by porphyrinic microsensor was altered. In contrast, transduction
enhanced NO production in non-atherosclerotic rat aorta and human
internal mammary artery. In transduced carotid artery, calcium-dependent
eNOS activity was minimal and did not differ from control
conditions. Vascular tetrahydrobiopterin concentrations did not differ between
the experimental groups.Treatment of transduced carotid artery with
FAD, FMN, NADPH, L-arginine, and either sepiapterin or tetrahydrobiopterin
did not alter NO release. Superoxide formation was similar in
transduced carotid artery and control. Treatment of transduced carotid
artery with superoxide dismutase (SOD), PEG-SOD, PEG-catalase did not affect
NO release. eNOS transduction in atherosclerotic human
carotid artery results in high expression without any measurable activity of
the recombinant protein. The defect in the atherosclerotic vessels is neither
caused by cofactor deficiency nor enhanced NO breakdown. Since angioplasty
is performed in atherosclerotic arteries,eNOS gene therapy is unlikely
to provide clinical benefit.
datePublished:2007-03-15T00:00:00Z
dateModified:2007-03-15T00:00:00Z
pageStart:308
pageEnd:317
sameAs:https://doi.org/10.1007/s00395-007-0650-7
keywords:
Nitric oxide synthase
gene therapy
adenoviral vector
atherosclerosis
endothelium
Cardiology
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