Accelerated Atherosclerosis by Placement of a Perivascular Cuff and a Cholesterol-Rich Diet in ApoE3Leiden Transgenic Mice

• Published in: Circulation research Vol. 87; no. 3; pp. 248 - 253
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 04.08.2000; Lippincott; Lippincott Williams & Wilkins Ovid Technologies
• Subjects: Animals; Apolipoprotein E3; Apolipoproteins E - genetics; Apolipoproteins E - physiology; Arteriosclerosis - etiology; Arteriosclerosis - genetics; Arteriosclerosis - pathology; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cholesterol - blood; Cholesterol, Dietary - toxicity; Constriction; Diet, Atherogenic; Femoral Artery - pathology; Genetic Predisposition to Disease; Hemorheology; Hypercholesterolemia - complications; Hypercholesterolemia - etiology; Hypercholesterolemia - genetics; Hyperplasia; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Transgenic; Point Mutation; Specific Pathogen-Free Organisms; Triglycerides - blood; Tunica Intima - pathology; Animal model; Hyperplasia; Transgenic animal; Cardiovascular disease; Lipids; Hyperlipoproteinemia; Supplemented diet; Foam cell; Vascular disease; Apolipoprotein E; Blood vessel; Atherosclerosis; Intima; Dyslipemia; Vascular wall; Thickening; Rodentia; Metabolic diseases; Cholesterol; Feeding; Vertebrata; Mammalia; Hypercholesterolemia; Mouse; Circulatory system
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.res.87.3.248

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.