In ApoE*3Leiden mice with a cuffed femoral artery, a highly cholesterol-rich diet resulted in a 7.8-fold increase in total intimal area compared to a chow diet at 14 days.
Does diet-induced hypercholesterolemia accelerate intimal hyperplasia after vascular injury in ApoE*3Leiden mice?
The combination of local vascular injury (cuff placement) and systemic hypercholesterolemia rapidly induces atherosclerotic-like lesions in ApoE*3Leiden mice within 14 days.
Effect estimate: 7.8-fold increase (high cholesterol) and 2.7-fold increase (mild cholesterol)
Intimal hyperplasia after vascular injury is usually studied in animal models with healthy, normocholesterolemic animals. Here, we assess the effect of diet-induced hypercholesterolemia on the induction of intimal hyperplasia in ApoE*3Leiden mice. A nonconstrictive polyethylene cuff was placed around the femoral artery of ApoE3*Leiden mice fed a highly cholesterol-rich diet, a mildly cholesterol-rich diet, or a chow diet for 4 weeks. Diets were continued after cuff placement until euthanization. At several time points (1 to 14 days), mice were euthanized and the intimal hyperplasia in the cuffed arteries was analyzed. In mice fed a chow diet, a 2- to 4-cell-layer-thick intima, predominantly consisting of alpha smooth muscle cell actin-positive cells, was observed after 14 days. A mildly cholesterol-rich diet (mean plasma-cholesterol level, 10.5 mmol/L) resulted in a 2.7-fold increase of total intimal area, and a highly cholesterol-rich diet (mean plasma cholesterol level 28. 6 mmol/L), in a 7.8-fold increase. In the high-cholesterol group, the intima consisted predominantly of lipid-loaded foam cells and alpha smooth muscle cell actin-positive cells. Foam cell accumulation could be observed by as early as 3 days, resulting in a near-total occlusion of the lumen after 14 days. Hypercholesterolemia resulted in a rapid, cholesterol-dependent induction of foam cell-rich intimal hyperplasia in cuffed femoral arteries of ApoE*3Leiden mice. In conclusion, the present data show that the combination of a local (cuff placement) and a systemic (hypercholesterolemic) risk factor of atherosclerosis results in a rapid induction (within 14 days) of atherosclerotic-like lesions in ApoE*3Leiden mice.
Lardenoye et al. (2000) studied Intimal hyperplasia and atherosclerosis. Cholesterol-rich diet (mild or high) with perivascular cuff vs. Chow diet with perivascular cuff was evaluated on Total intimal area (intimal hyperplasia) (7.8-fold increase (high cholesterol) and 2.7-fold increase (mild cholesterol)). In ApoE*3Leiden mice with a cuffed femoral artery, a highly cholesterol-rich diet resulted in a 7.8-fold increase in total intimal area compared to a chow diet at 14 days.