Accelerated atherosclerosis by placement of a perivascular cuff and a cholesterol-rich diet in ApoE*3Leiden transgenic mice

Accelerated atherosclerosis by placement of a perivascular cuff and a cholesterol-rich diet in ApoE*3Leiden transgenic mice

Lardenoye, J.H.P.
Delsing, D.J.M.
de Vries, M.R.
Deckers, M.M.L.
Princen, H.M.G.
Havekes, L.M.
van Hinsbergh, V.W.M.
van Bockel, J.H.
Quax, P.H.A.
Gaubius Instituut TNO

2000

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 α 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 α 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. Chemicals/CAS: Apolipoprotein E3; Apolipoproteins E; Cholesterol, 57-88-5; Cholesterol, Dietary; Triglycerides

Biology
Animals
Apolipoprotein E3
Apolipoproteins E
Arteriosclerosis
Cholesterol
Cholesterol, Dietary
Constriction
Diet, Atherogenic
Femoral Artery
Genetic Predisposition to Disease
Hemorheology
Hypercholesterolemia
Hyperplasia
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Point Mutation
Specific Pathogen-Free Organisms
Triglycerides
Tunica Intima

http://resolver.tudelft.nl/uuid:c7dd5103-9454-4e9a-81e5-5d5e79ed9ad4

235645

0009-7330

Circulation Research, 87 (3), 248-253

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