Source:http://linkedlifedata.com/resource/pubmed/id/14630804
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7
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pubmed:dateCreated |
2004-3-22
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pubmed:abstractText |
Deficiency of methylenetetrahydrofolate reductase (MTHFR) predisposes to hyperhomocysteinemia and vascular disease. We tested the hypothesis that heterozygous disruption of the Mthfr gene sensitizes mice to diet-induced hyperhomocysteinemia and endothelial dysfunction. Mthfr(+/-) and Mthfr(+/+) mice were fed 1 of 4 diets: control, high methionine (HM), low folate (LF), or high methionine/low folate (HM/LF). Plasma total homocysteine (tHcy) was higher with the LF and HM/LF diets than the control (P<.01) or HM (P<.05) diets, and Mthfr(+/-) mice had higher tHcy than Mthfr(+/+) mice (P<.05). With the control diet, the S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH) ratio was lower in the liver and brain of Mthfr(+/-) mice than Mthfr(+/+) mice (P<.05). SAM/SAH ratios decreased further in Mthfr(+/+) or Mthfr(+/-) mice fed LF or LF/HM diets (P<.05). In cerebral arterioles, endothelium-dependent dilation to 1 or 10 microM acetylcholine was markedly and selectively impaired with the HM/LF diet compared with the control diet for both Mthfr(+/+) (maximum dilation 5% +/- 2% versus 21% +/- 4%; P<.01) and Mthfr(+/-) (6% +/- 2% versus 21% +/- 3%; P<.01) mice. These findings demonstrate that the Mthfr(+/-) genotype sensitizes mice to diet-induced hyperhomocysteinemia and that hyperhomocysteinemia alters tissue methylation capacity and impairs endothelial function in cerebral microvessels.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Choline,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine,
http://linkedlifedata.com/resource/pubmed/chemical/Methionine,
http://linkedlifedata.com/resource/pubmed/chemical/Methylenetetrahydrofolate...,
http://linkedlifedata.com/resource/pubmed/chemical/Vitamin B Complex
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0006-4971
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
103
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2624-9
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:14630804-Animals,
pubmed-meshheading:14630804-Aorta,
pubmed-meshheading:14630804-Arterioles,
pubmed-meshheading:14630804-Cerebral Arteries,
pubmed-meshheading:14630804-Choline,
pubmed-meshheading:14630804-Crosses, Genetic,
pubmed-meshheading:14630804-Cysteine,
pubmed-meshheading:14630804-Diet,
pubmed-meshheading:14630804-Endothelium, Vascular,
pubmed-meshheading:14630804-Genotype,
pubmed-meshheading:14630804-Hyperhomocysteinemia,
pubmed-meshheading:14630804-Methionine,
pubmed-meshheading:14630804-Methylenetetrahydrofolate Reductase (NADPH2),
pubmed-meshheading:14630804-Mice,
pubmed-meshheading:14630804-Mice, Inbred BALB C,
pubmed-meshheading:14630804-Mice, Knockout,
pubmed-meshheading:14630804-Muscle, Smooth, Vascular,
pubmed-meshheading:14630804-Vitamin B Complex
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pubmed:year |
2004
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pubmed:articleTitle |
Effect of Mthfr genotype on diet-induced hyperhomocysteinemia and vascular function in mice.
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pubmed:affiliation |
Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City 52242, USA.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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