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

Content Provider	Semantic Scholar
Author	Lardenoye, J. H. P. Princen, Hans M. G.
Copyright Year	2000
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 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.
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Alternate Webpage(s)	http://circres.ahajournals.org/content/circresaha/87/3/248.full.pdf?download=true
Alternate Webpage(s)	http://circres.ahajournals.org/content/circresaha/87/3/248.full.pdf
PubMed reference number	10926877v1
Volume Number	87
Issue Number	3
Journal	Circulation research
Language	English
Access Restriction	Open
Subject Keyword	Animal Model Atherosclerosis Cholesterol measurement test Congenital adrenal hyperplasia Hypercholesterolemia Muscle Cells Myocytes, Smooth Muscle Polyethylene Glycols Polyethylenes Smooth muscle (tissue) Structure of femoral artery Structure of lumen of body system Vascular System Injuries chow chow
Content Type	Text
Resource Type	Article