Journal article
Prothrombotic effects of hyperhomocysteinemia and hypercholesterolemia in ApoE-deficient mice
Arteriosclerosis, thrombosis, and vascular biology, Vol.27(1), pp.233-240
2007
DOI: 10.1161/01.ATV.0000251607.96118.af
PMID: 17082485
Abstract
Objective: We tested the hypothesis that hyperhomocysteinemia and hypercholesterolemia promote arterial thrombosis in mice.
Methods and results: Male apolipoprotein E (Apoe)-deficient mice were fed one of four diets: control, hyperhomocysteinemic (HH), high fat (HF), or high fat/hyperhomocysteinemic (HF/HH). Total cholesterol was elevated 2-fold with the HF or HF/HH diets compared with the control or HH diets (P<0.001). Plasma total homocysteine (tHcy) was elevated (12 to 15 micromol/L) with the HH or HF/HH diets compared with the control or HF diets (4 to 6 micromol/L; P<0.001). Aortic sinus lesion area correlated strongly with total cholesterol (P<0.001) but was independent of tHcy. At 12 weeks of age, the time to thrombotic occlusion of the carotid artery after photochemical injury was >50% shorter in mice fed the HF diets, with or without hyperhomocysteinemia, compared with the control diet (P<0.05). At 24 weeks of age, carotid artery thrombosis was also accelerated in mice fed the HH diet (P<0.05). Endothelium-dependent nitric oxide-mediated relaxation of carotid artery rings was impaired in mice fed the HF, HH, or HF/HH diets compared with the control diet (P<0.05).
Conclusions: Hyperhomocysteinemia and hypercholesterolemia, alone or in combination, produce endothelial dysfunction and increased susceptibility to thrombosis in Apoe-deficient mice.
Details
- Title: Subtitle
- Prothrombotic effects of hyperhomocysteinemia and hypercholesterolemia in ApoE-deficient mice
- Creators
- Katina M WILSON - Department of Internal Medicine, The University of Iowa Carver College of Medicine, Iowa City, United StatesRyan B MCCAW - Department of Internal Medicine, The University of Iowa Carver College of Medicine, Iowa City, United StatesLorie LEO - Department of Internal Medicine, The University of Iowa Carver College of Medicine, Iowa City, United StatesErland ARNING - Baylor Institute of Metabolic Disease, Dallas, Tex, United StatesSarka LHOTAK - McMaster University, Hamilton, Ontario, United StatesTeodoro BOTTIGLIERI - Baylor Institute of Metabolic Disease, Dallas, Tex, United StatesRichard C AUSTIN - McMaster University, Hamilton, Ontario, United StatesSteven R LENTZ - Department of Internal Medicine, The University of Iowa Carver College of Medicine, Iowa City, United States
- Resource Type
- Journal article
- Publication Details
- Arteriosclerosis, thrombosis, and vascular biology, Vol.27(1), pp.233-240
- Publisher
- Lippincott
- DOI
- 10.1161/01.ATV.0000251607.96118.af
- PMID
- 17082485
- ISSN
- 1079-5642
- eISSN
- 1524-4636
- Language
- English
- Date published
- 2007
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984094563602771
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