Abstract
Cerebral Vascular Dysfunction in Methionine Synthase-Deficient Mice
Blood, Vol.104(11), pp.2617-2617
11/16/2004
DOI: 10.1182/blood.V104.11.2617.2617
Abstract
Abstract
Methionine synthase (MS) is a key enzyme involved in remethylation of homocysteine to methionine. We tested the hypothesis that deficiency of MS influences endothelial function. Mice heterozygous for disruption of the Ms gene (Ms+/−), and wild type littermates (Ms+/+), were fed either a control diet or a low folate (LF) diet. Plasma total homocysteine was similar in Ms+/+ and Ms+/− mice fed the control diet (4.5±0.3 and 5.3±0.4 μmol/L, respectively), and was mildly elevated in Ms+/+ or Ms+/− mice fed the LF diet (7.5±0.7 and 9.6±1.2 μmol/L, respectively; p<0.001 vs. control diet). Dilatation of cerebral arterioles (~30 μm diameter) to the endothelium-dependent dilator, acetylcholine (10 μM), was blunted in Ms+/− mice compared with Ms+/+ mice fed the control diet (21±4 vs. 32±4%; p<0.05). Both Ms+/+ and Ms+/− mice exhibited impaired dilatation of cerebral arterioles to acetylcholine when they were fed the LF diet (12±2 and 17±3%, respectively; p<0.01 vs. Ms+/+ mice fed the control diet). Dilatation of cerebral arterioles in response to the endothelium-independent dilator, nitroprusside, was similar in all groups of mice. Relaxation of aortic rings to acetylcholine was not influenced by Ms genotype or diet. Elevated levels of superoxide and hydrogen peroxide were detected by dihydroethidium (DHE) and dichlorodihydrofluorescein (DCF), respectively, in cerebral arterioles of Ms+/− mice fed the control diet and in both Ms+/+ and Ms+/− mice fed the LF diet. These findings demonstrate that defective homocysteine remethylation caused by deficiency of either MS or folate produces endothelial dysfunction and increased oxidative stress in the cerebral microcirculation of mice. Interestingly, impairment of cerebral vascular function was independent of plasma tHcy concentration.
Details
- Title: Subtitle
- Cerebral Vascular Dysfunction in Methionine Synthase-Deficient Mice
- Creators
- Sanjana Dayal - University of IowaAngela M. Devlin - University of IowaRyan B. McCaw - University of IowaMei-lan Liu - University of California, BerkeleyErland Arning - Baylor UniversityTeodoro Bottiglieri - Baylor UniversityBarry Shane - University of California, BerkeleyFrank M. Faraci - University of IowaSteven R. Lentz - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Blood, Vol.104(11), pp.2617-2617
- DOI
- 10.1182/blood.V104.11.2617.2617
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Language
- English
- Date published
- 11/16/2004
- Academic Unit
- Cardiovascular Medicine; Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine; Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
- Record Identifier
- 9984304751002771
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