Journal article
Endothelial dysfunction and elevation of s-adenosylhomocysteine in cystathionine β-synthase-deficient mice
Circulation research, Vol.88(11), pp.1203-1209
2001
DOI: 10.1161/hh1101.092180
PMID: 11397788
Abstract
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.
Details
- Title: Subtitle
- Endothelial dysfunction and elevation of s-adenosylhomocysteine in cystathionine β-synthase-deficient mice
- Creators
- Sanjana DAYAL - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa, United StatesTeodoro BOTTIGLIERI - Veterans Affairs Medical Center, Iowa City, Iowa, United StatesErland ARNING - Veterans Affairs Medical Center, Iowa City, Iowa, United StatesNobuyo MAEDA - Baylor Instituteof Metabolic Disease, Dallas, Tex, United StatesM. René Malinow - Oregon RegionalPrimate Research Center, Beaverton, Oreg., United StatesCurt D SIGMUND - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa, United StatesDonald D HEISTAD - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa, United StatesFrank M FARACI - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa, United StatesSteven R LENTZ - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa, United States
- Resource Type
- Journal article
- Publication Details
- Circulation research, Vol.88(11), pp.1203-1209
- DOI
- 10.1161/hh1101.092180
- PMID
- 11397788
- NLM abbreviation
- Circ Res
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Publisher
- Lippincott; Hagerstown, MD
- Language
- English
- Date published
- 2001
- Academic Unit
- Molecular Physiology and Biophysics; Hematology, Oncology, and Blood & Marrow Transplantation; Iowa Neuroscience Institute; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040473602771
Metrics
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