© 2000 American Heart Association, Inc.
Integrative Physiology |
Accelerated Atherosclerosis by Placement of a Perivascular Cuff and a Cholesterol-Rich Diet in ApoE*3Leiden Transgenic Mice
From the Gaubius Laboratory (J.H.P.L., D.J.M.D., M.R.d.V., H.M.G.P., L.M.H., V.W.M.v.H., P.H.A.Q.) and Leiden University Medical Center (J.H.P.L., M.M.L.D., L.M.H., J.H.v.B.), Leiden, the Netherlands.
Correspondence to Dr P.H.A. Quax, Gaubius Laboratory TNO-PG, PO Box 2215, 2301 CE Leiden, the Netherlands. E-mail pha.quax{at}pg.tno.nl
Abstract—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 
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 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.
Key Words: atherosclerosis • foam cell accumulation • transgenic mice • intimal hyperplasia
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