Journal article
Enhanced susceptibility to arterial thrombosis in a murine model of hyperhomocysteinemia
Blood, Vol.108(7), pp.2237-2243
10/01/2006
DOI: 10.1182/blood-2006-02-005991
PMCID: PMC1895559
PMID: 16804115
Abstract
Hyperhomocysteinemia is a risk factor for thrombosis, but the mechanisms are not well defined. We tested the hypothesis that hyperhomocysteinemia accelerates arterial thrombosis in mice. Mice heterozygous for a targeted disruption of the cystathionine β-synthase gene (
Cbs
+/–
) and wild-type littermates (
Cbs
+/+
) were fed either a control diet or a high methionine/low folate (HM/LF) diet for 6 to 8 months to produce graded hyperhomocysteinemia. The time to occlusion of the carotid artery after photochemical injury was shortened by more than 50% in
Cbs
+/+
or
Cbs
+/–
mice fed the HM/LF diet (
P
< .001 versus control diet). Carotid artery thrombosis was not accelerated in mice deficient in endothelial nitric oxide synthase
(Nos3)
, which suggests that decreased endothelium-derived nitric oxide is not a sufficient mechanism for enhancement of thrombosis.
Cbs
+
/
+
and
Cbs
+/–
mice fed the HM/LF diet had elevated levels of reactive oxygen species in the carotid artery, increased aortic expression of the NADPH oxidase catalytic subunit, Nox4, and decreased activation of anticoagulant protein C in the aorta (
P
< .05 versus control diet). We conclude that hyperhomocysteinemia enhances susceptibility to arterial thrombosis through a mechanism that is not caused by loss of endothelium-derived nitric oxide but may involve oxidative stress and impairment of the protein C anticoagulant pathway.
Details
- Title: Subtitle
- Enhanced susceptibility to arterial thrombosis in a murine model of hyperhomocysteinemia
- Creators
- Sanjana Dayal - From the Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City; Baylor Institute of Metabolic Disease, Dallas, TX; and Veterans Affairs Medical Center, Iowa City, IAKatina M Wilson - From the Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City; Baylor Institute of Metabolic Disease, Dallas, TX; and Veterans Affairs Medical Center, Iowa City, IALorie Leo - From the Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City; Baylor Institute of Metabolic Disease, Dallas, TX; and Veterans Affairs Medical Center, Iowa City, IAErland Arning - From the Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City; Baylor Institute of Metabolic Disease, Dallas, TX; and Veterans Affairs Medical Center, Iowa City, IATeodoro Bottiglieri - From the Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City; Baylor Institute of Metabolic Disease, Dallas, TX; and Veterans Affairs Medical Center, Iowa City, IASteven R Lentz - From the Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City; Baylor Institute of Metabolic Disease, Dallas, TX; and Veterans Affairs Medical Center, Iowa City, IA
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.108(7), pp.2237-2243
- Publisher
- The American Society of Hematology
- DOI
- 10.1182/blood-2006-02-005991
- PMID
- 16804115
- PMCID
- PMC1895559
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Language
- English
- Date published
- 10/01/2006
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984065484202771
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