Prothrombotic Effects of Hyperhomocysteinemia and Hypercholesterolemia in ApoE-Deficient Mice Journal Articles uri icon

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  • 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 μmol/L) with the HH or HF/HH diets compared with the control or HF diets (4 to 6 μmol/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.


  • Wilson, Katina M
  • McCaw, Ryan B
  • Leo, Lorie
  • Arning, Erland
  • Lhoták, Šárka
  • Bottiglieri, Teodoro
  • Austin, Richard C
  • Lentz, Steven R

publication date

  • January 2007

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