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Updated: Jul 19, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
Prothrombotic effects of hyperhomocysteinemia and hypercholesterolemia in ApoE-deficient mice
Katina M Wilson1, Ryan B McCaw, Lorie Leo
1Department of Internal Medicine, The University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
Insights
High cholesterol and high homocysteine levels accelerate arterial thrombosis and cause endothelial dysfunction in mice. These conditions, alone or combined, increase the risk of blood clots in arteries.
Area of Science:
- Cardiovascular Science
- Thrombosis Research
- Atherosclerosis Studies
Background:
- Hyperhomocysteinemia and hypercholesterolemia are risk factors for cardiovascular disease.
- The combined effects of these conditions on arterial thrombosis are not fully understood.
Purpose of the Study:
- To investigate the hypothesis that hyperhomocysteinemia and hypercholesterolemia promote arterial thrombosis.
- To assess the impact of these conditions on endothelial function.
Main Methods:
- Apolipoprotein E (Apoe)-deficient mice were fed control, hyperhomocysteinemic (HH), high fat (HF), or HF/HH diets.
- Plasma lipid and homocysteine levels were measured.
- Aortic sinus lesion area and carotid artery thrombosis time after photochemical injury were assessed.
- Endothelium-dependent vasodilation was evaluated in carotid artery rings.
Main Results:
- HF and HF/HH diets significantly elevated total cholesterol.
- HH and HF/HH diets significantly elevated plasma total homocysteine (tHcy).
- Aortic lesion area correlated with cholesterol but not tHcy.
- Carotid artery thrombosis was accelerated in mice on HF diets (with or without HH) and HH diets.
- Endothelial function was impaired in mice on HF, HH, or HF/HH diets.
Conclusions:
- Hyperhomocysteinemia and hypercholesterolemia independently and synergistically impair endothelial function.
- These metabolic disturbances increase susceptibility to arterial thrombosis in Apoe-deficient mice.
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.
