Journal article
Folate dependence of hyperhomocysteinemia and vascular dysfunction in cystathionine β-synthase-deficient mice
American journal of physiology. Heart and circulatory physiology, Vol.279(3), pp.H970-H975
09/01/2000
DOI: 10.1152/ajpheart.2000.279.3.H970
PMID: 10993757
Abstract
Hyperhomocysteinemia is a risk factor for stroke, myocardial infarction, and venous thrombosis. Moderate hyperhomocysteinemia is associated with impaired endothelial function, but the mechanisms responsible for endothelial dysfunction in hyperhomocysteinemia are poorly understood. We have used genetic and dietary approaches to produce hyperhomocysteinemia in mice. Heterozygous cystathionine β-synthase-deficient mice (CBS +/−), which have a selective defect in homocysteine transsulfuration, and wild-type (CBS +/+) littermates were fed either a control diet or a diet that is relatively deficient in folic acid for 6 wk. Plasma total homocysteine was 5.3 ± 0.7 μM in CBS +/+ mice and 6.4 ± 0.6 μM in CBS +/− mice ( P = 0.3) given the control diet. Plasma total homocysteine was 11.6 ± 4.5 μM in CBS +/+ mice and 25.1 ± 3.2 μM in CBS +/− mice ( P = 0.004) given a low-folate diet. In mice fed the control diet, relaxation of aortic rings in response to the endothelium-dependent vasodilator acetylcholine did not differ significantly between CBS +/+ mice and CBS +/− mice. In contrast, in mice fed a low-folate diet, maximal relaxation to acetylcholine was markedly impaired in CBS +/− mice (58 ± 9%) compared with CBS +/+ mice (84 ± 4%) ( P = 0.01). No differences in relaxation to the endothelium-independent vasodilator sodium nitroprusside were observed among the four groups of mice. These data indicate that CBS-deficient mice are predisposed to hyperhomocysteinemia during dietary folate deficiency, and moderate hyperhomocysteinemia is associated with marked impairment of endothelial function in mice.
Details
- Title: Subtitle
- Folate dependence of hyperhomocysteinemia and vascular dysfunction in cystathionine β-synthase-deficient mice
- Creators
- Steven R Lentz - Veterans Affairs Medical Center, Iowa City 52246; Departments of, Internal Medicine andRochelle A Erger - Veterans Affairs Medical Center, Iowa City 52246; Departments ofSanjana Dayal - Internal Medicine andNobuyo Maeda - Department of Pathology, University of North Carolina, Chapel Hill, North Carolina 27599; andM. René Malinow - Oregon Regional Primate Research Center, Beaverton, Oregon 97006Donald D Heistad - Veterans Affairs Medical Center, Iowa City 52246; Departments of, Internal Medicine and, Pharmacology, University of Iowa College of Medicine, Iowa City, Iowa 52242Frank M Faraci - Internal Medicine and, Pharmacology, University of Iowa College of Medicine, Iowa City, Iowa 52242
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Heart and circulatory physiology, Vol.279(3), pp.H970-H975
- DOI
- 10.1152/ajpheart.2000.279.3.H970
- PMID
- 10993757
- ISSN
- 0363-6135
- eISSN
- 1522-1539
- Language
- English
- Date published
- 09/01/2000
- Academic Unit
- 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
- 9984040434302771
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