Journal article
Hyperhomocysteinemic Mice Have Increased Susceptibility to Carotid Artery Thrombosis
Blood, Vol.104(11), pp.2616-2616
11/16/2004
DOI: 10.1182/blood.V104.11.2616.2616
Abstract
Abstract Hyperhomocysteinemia is a risk factor for cardiovascular disease, stroke, and venous thrombosis. In animal models, hyperhomocysteinemia produces endothelial dysfunction due to decreased bioavailability of endothelium-derived nitric oxide (NO). Because NO has antithrombotic properties, we tested the hypothesis that hyperhomocysteinemia accelerates photochemically-induced carotid artery thrombosis induced in mice. Mice heterozygous for a targeted disruption of the cystathionine β-synthase (Cbs) gene (Cbs+/−) and wild type littermates (Cbs+/+) were fed either a control diet or a high methionine/low folate (HM/LF) diet for 8 months. Plasma total homocysteine was elevated by the HM/LF diet compared with the control diet in both Cbs+/+ (11.6±1.2 vs. 3.7±0.5 μmol/L; p<0.05) and Cbs+/− mice (26.4±3.8 vs. 6.2±0.6 μmol/L; p<0.001). The time to stable occlusion after photochemical injury (rose bengal and green laser) of the carotid artery was 50% shorter in mice fed the HM/HF diet (17.5±2.3 and 18.2±4.0 minutes for Cbs+/+ and Cbs+/− mice, respectively) compared with mice fed the control diet (44.0±9.1 and 31.4±4.7 minutes for Cbs+/+ and Cbs+/− mice, respectively; p<0.001). Using the oxidative dye, dihydroethidium (DHE), increased production of superoxide was detected in Cbs+/+ and Cbs+/− mice fed the HF/HM diet compared with the control diet. To determine whether lack of endothelium-derived NO may accelerate carotid artery thrombosis, mice deficient in endothelial nitric oxide synthase (Nos3−/ −) were also studied. Time to occlusion did not differ between Nos3−/ − mice and wild type mice (55.0±10.2 vs. 42.1±7.1 minutes, p=0.31). We conclude that hyperhomcysteinemia increases susceptibility to experimental thrombosis through a mechanism that is independent of endothelium-derived NO, but may involve oxidative stress.
Details
- Title: Subtitle
- Hyperhomocysteinemic Mice Have Increased Susceptibility to Carotid Artery Thrombosis
- Creators
- Katina M Wilson - Internal Medicine, The University of Iowa, Iowa City, IA, USASanjana Dayal - Internal Medicine, The University of Iowa, Iowa City, IA, USATeodoro Bottiglieri - Baylor Institute of Metabolic Disease, Dallas, TX, USASteven R Lentz - Internal Medicine, The University of Iowa, Iowa City, IA, USA
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.104(11), pp.2616-2616
- DOI
- 10.1182/blood.V104.11.2616.2616
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Language
- English
- Date published
- 11/16/2004
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine; Iowa Neuroscience Institute
- Record Identifier
- 9984071641802771
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