Journal article
Effect of Mthfr genotype on diet-induced hyperhomocysteinemia and vascular function in mice
Blood, Vol.103(7), pp.2624-2629
04/01/2004
DOI: 10.1182/blood-2003-09-3078
PMID: 14630804
Abstract
Abstract 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 μM 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.
Details
- Title: Subtitle
- Effect of Mthfr genotype on diet-induced hyperhomocysteinemia and vascular function in mice
- Creators
- Angela M Devlin - From the Departments of Internal Medicine and Pharmacology, University of Iowa Carver College of Medicine, Iowa City; Veterans Affairs Medical Center, Iowa City, IA; Baylor Institute of Metabolic Disease, Dallas, TX; and Montreal Children's Hospital Research Institute, McGill University, Montreal, QC, CanadaErland Arning - From the Departments of Internal Medicine and Pharmacology, University of Iowa Carver College of Medicine, Iowa City; Veterans Affairs Medical Center, Iowa City, IA; Baylor Institute of Metabolic Disease, Dallas, TX; and Montreal Children's Hospital Research Institute, McGill University, Montreal, QC, CanadaTeodoro Bottiglieri - From the Departments of Internal Medicine and Pharmacology, University of Iowa Carver College of Medicine, Iowa City; Veterans Affairs Medical Center, Iowa City, IA; Baylor Institute of Metabolic Disease, Dallas, TX; and Montreal Children's Hospital Research Institute, McGill University, Montreal, QC, CanadaFrank M Faraci - From the Departments of Internal Medicine and Pharmacology, University of Iowa Carver College of Medicine, Iowa City; Veterans Affairs Medical Center, Iowa City, IA; Baylor Institute of Metabolic Disease, Dallas, TX; and Montreal Children's Hospital Research Institute, McGill University, Montreal, QC, CanadaRima Rozen - From the Departments of Internal Medicine and Pharmacology, University of Iowa Carver College of Medicine, Iowa City; Veterans Affairs Medical Center, Iowa City, IA; Baylor Institute of Metabolic Disease, Dallas, TX; and Montreal Children's Hospital Research Institute, McGill University, Montreal, QC, CanadaSteven R Lentz - From the Departments of Internal Medicine and Pharmacology, University of Iowa Carver College of Medicine, Iowa City; Veterans Affairs Medical Center, Iowa City, IA; Baylor Institute of Metabolic Disease, Dallas, TX; and Montreal Children's Hospital Research Institute, McGill University, Montreal, QC, Canada
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.103(7), pp.2624-2629
- DOI
- 10.1182/blood-2003-09-3078
- PMID
- 14630804
- NLM abbreviation
- Blood
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Language
- English
- Date published
- 04/01/2004
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040377302771
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