Linked Life Data

11397788

Source:http://linkedlifedata.com/resource/pubmed/id/11397788

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2001-6-8
pubmed:abstractText
Hyperhomocysteinemia is associated with increased risk for cardiovascular events, but it is not certain whether it is a mediator of vascular dysfunction or a marker for another risk factor. Homocysteine levels are regulated by folate bioavailability and also by the methyl donor S-adenosylmethionine (SAM) and its metabolite S-adenosylhomocysteine (SAH). We tested the hypotheses that endothelial dysfunction occurs in hyperhomocysteinemic mice in the absence of folate deficiency and that levels of SAM and SAH are altered in mice with dysfunction. Heterozygous cystathionine beta-synthase-deficient (CBS(+/-)) and wild-type (CBS(+/+)) mice were fed a folate-replete, methionine-enriched diet. Plasma levels of total homocysteine were elevated in CBS(+/-) mice compared with CBS(+/+) mice after 7 weeks (27.1+/-5.2 versus 8.8+/-1.1 micromol/L; P<0.001) and 15 weeks (23.9+/-3.0 versus 13.0+/-2.3 micromol/L; P<0.01). After 15 weeks, but not 7 weeks, relaxation of aortic rings to acetylcholine was selectively impaired by 35% (P<0.05) and thrombomodulin anticoagulant activity was decreased by 20% (P<0.05) in CBS(+/-) mice. Plasma levels of folate did not differ between groups. Levels of SAH were elevated approximately 2-fold in liver and brain of CBS(+/-) mice, and correlations were observed between plasma total homocysteine and SAH in liver (r=0.54; P<0.001) and brain (r=0.67; P<0.001). These results indicate that endothelial dysfunction occurs in hyperhomocysteinemic mice even in the absence of folate deficiency. Endothelial dysfunction in CBS(+/-) mice was associated with increased tissue levels of SAH, which suggests that altered SAM-dependent methylation may contribute to vascular dysfunction in hyperhomocysteinemia.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
8
pubmed:volume
88
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1203-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11397788-Animals, pubmed-meshheading:11397788-Aorta, pubmed-meshheading:11397788-Brain, pubmed-meshheading:11397788-Chronic Disease, pubmed-meshheading:11397788-Cystathionine beta-Synthase, pubmed-meshheading:11397788-Disease Models, Animal, pubmed-meshheading:11397788-Endothelium, Vascular, pubmed-meshheading:11397788-Folic Acid, pubmed-meshheading:11397788-Food, Fortified, pubmed-meshheading:11397788-Heterozygote, pubmed-meshheading:11397788-Homocysteine, pubmed-meshheading:11397788-Hyperhomocysteinemia, pubmed-meshheading:11397788-Liver, pubmed-meshheading:11397788-Methionine, pubmed-meshheading:11397788-Methylation, pubmed-meshheading:11397788-Mice, pubmed-meshheading:11397788-Mice, Inbred C57BL, pubmed-meshheading:11397788-Mice, Knockout, pubmed-meshheading:11397788-S-Adenosylhomocysteine, pubmed-meshheading:11397788-S-Adenosylmethionine, pubmed-meshheading:11397788-Thrombomodulin, pubmed-meshheading:11397788-Vasoconstrictor Agents, pubmed-meshheading:11397788-Vasodilator Agents, pubmed-meshheading:11397788-Vasomotor System
pubmed:year
2001
pubmed:articleTitle
Endothelial dysfunction and elevation of S-adenosylhomocysteine in cystathionine beta-synthase-deficient mice.
pubmed:affiliation
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa, USA.
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