Blockade of endothelin receptors markedly reduces atherosclerosis in LDL receptor deficient mice : role of endothelin in macrophage foam cell formation

We evaluated the direct effects of long-term blockade of ET(A) and ET(B) receptors using a mixed endothelin (ET) receptor antagonist, LU224332, in the low density lipoprotein receptor (LDL-R) knockout mouse model of atherosclerosis. Four groups of LDL-R deficient mice were studied: control mice fed...

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Bibliographic Details
Published in:Cardiovascular research 2000-10, Vol.48 (1), p.158-167
Main Authors: BABAEI, Saeid, PICARD, Pierre, RAVANDI, Amir, MONGE, Juan Carlos, LEE, Tony C, CERNACEK, Peter, STEWART, Duncan J
Format: Article
Language:English
Subjects:
Animals
Arteriosclerosis - metabolism
Arteriosclerosis - pathology
Atherosclerosis (general aspects, experimental research)
Biological and medical sciences
Blood and lymphatic vessels
Cardiology. Vascular system
Endothelin Receptor Antagonists
Endothelins - physiology
Foam Cells - metabolism
Foam Cells - pathology
Hyperlipidemias - metabolism
Hyperlipidemias - pathology
Male
Medical sciences
Mice
Mice, Inbred C57BL
Mice, Knockout
Models, Animal
Propionates - pharmacology
Pyrimidines - pharmacology
Receptors, LDL - deficiency
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Summary:We evaluated the direct effects of long-term blockade of ET(A) and ET(B) receptors using a mixed endothelin (ET) receptor antagonist, LU224332, in the low density lipoprotein receptor (LDL-R) knockout mouse model of atherosclerosis. Four groups of LDL-R deficient mice were studied: control mice fed normal chow (group I); mice fed a high cholesterol (HC, 1.25%) diet alone (group II), HC fed animals treated with LU224332 (group III); and mice fed normal chow treated with the LU compound (group IV). All treatments were continued for 8 weeks at which time the animals were sacrificed and the aortae were removed and stained with oil red O. Atherosclerotic area (AA) was determined by quantitative morphometry and normalized relative to total aortic area (TA). Cholesterol feeding resulted in a marked increased in total plasma cholesterol ( approximately 15 fold) and widespread aortic atherosclerosis (AA/TA: group I: 0.013+/-0.007; group II: 0.33+/-0. 11; P
ISSN:0008-6363
1755-3245
DOI:10.1016/s0008-6363(00)00169-3