Source:http://linkedlifedata.com/resource/pubmed/id/21166924
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2010-12-24
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pubmed:abstractText |
Oxidized low-density lipoprotein (OxLDL) causes impairment of endothelium-dependent, nitric oxide (NO)-mediated vasodilation involving l-arginine deficiency. However, the underlying mechanism remains elusive. Since arginase and endothelial NO synthase (eNOS) share the substrate l-arginine, we hypothesized that OxLDL may reduce l-arginine availability to eNOS for NO production, and thus vasodilation, by up-regulating arginase. To test this hypothesis, porcine subepicardial arterioles (70-130 ?m) were isolated for vasomotor study and for immunohistochemical detection of arginase and eNOS expressions. The coronary arterioles dilated dose-dependently to the endothelium-dependent NO-mediated vasodilator serotonin. This vasodilation was inhibited in the same manner by NOS inhibitor N(G)-nitro-l-arginine methyl ester and by lumenal OxLDL (0.5 mg protein/mL). The inhibitory effect of OxLDL was reversed after treating the vessels with either l-arginine (3 mM) or arginase inhibitor difluoromethylornithine (DFMO; 0.4 mM). Consistent with vasomotor alterations, OxLDL inhibited serotonin-induced NO release from coronary arterioles and this inhibition was reversed by DFMO. Vascular arginase activity was significantly elevated by OxLDL. Immunohistochemical analysis indicated that OxLDL increased arginase I expression in the vascular wall without altering eNOS expression. Taken together, these results suggest that OxLDL up-regulates arginase I, which contributes to endothelial dysfunction by reducing l-arginine availability to eNOS for NO production and thus vasodilation.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Arginase,
http://linkedlifedata.com/resource/pubmed/chemical/Arginine,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoproteins, LDL,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type III,
http://linkedlifedata.com/resource/pubmed/chemical/oxidized low density lipoprotein
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1549-8719
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pubmed:author | |
pubmed:copyrightInfo |
© 2010 John Wiley & Sons Ltd.
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pubmed:issnType |
Electronic
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
36-45
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pubmed:dateRevised |
2011-9-26
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pubmed:meshHeading |
pubmed-meshheading:21166924-Animals,
pubmed-meshheading:21166924-Arginase,
pubmed-meshheading:21166924-Arginine,
pubmed-meshheading:21166924-Coronary Vessels,
pubmed-meshheading:21166924-Enzyme Inhibitors,
pubmed-meshheading:21166924-Female,
pubmed-meshheading:21166924-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:21166924-Lipoproteins, LDL,
pubmed-meshheading:21166924-Male,
pubmed-meshheading:21166924-Nitric Oxide,
pubmed-meshheading:21166924-Nitric Oxide Synthase Type III,
pubmed-meshheading:21166924-Swine,
pubmed-meshheading:21166924-Up-Regulation,
pubmed-meshheading:21166924-Vasodilation
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pubmed:year |
2011
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pubmed:articleTitle |
Oxidized low-density lipoprotein inhibits nitric oxide-mediated coronary arteriolar dilation by up-regulating endothelial arginase I.
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pubmed:affiliation |
Department of Systems Biology and Translational Medicine, College of Medicine, Texas A&M Health Science Center, Temple, Texas 76504, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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