Prothrombotic Effects of Hyperhomocysteinemia and Hypercholesterolemia 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 P P 50% shorter in mice fed the HF diets, with or without hyperhomocysteinemia, compared with the control diet ( P P P Conclusions— Hyperhomocysteinemia and hypercholesterolemia, alone or in combination, produce endothelial dysfunction and increased susceptibility to thrombosis in Apoe-deficient mice.