Document Detail


Impairment of endothelium-dependent arterial relaxation by high-fat feeding in ApoE-deficient mice: toward normalization by human ApoA-I expression.
MedLine Citation:
PMID:  10484545     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Atherogenic lipoproteins can impair the endothelium-dependent arterial relaxation, and circumstantial evidence suggests a beneficial role of plasma high density lipoproteins and apolipoprotein (apo) A-I in counteracting the endothelium dysfunction. In the present study, vascular reactivity was determined in control, apoE-deficient mice (apoE-KO mice), and apoE-deficient mice expressing human apoA-I (apoE-KO/HuAITg mice). METHODS AND RESULTS: In the first part of the study, control and apoE-KO mice were fed a low-fat or a high-fat diet for 23 weeks, and the vasoactive responses of isolated thoracic aortic segments to norepinephrine, sodium nitroprusside, and acetylcholine (ACh) were determined. Whereas norepinephrine, sodium nitroprusside, and ACh evoked similar vascular responses in control and apoE-KO mice fed the low-fat diet, high-fat feeding in apoE-KO mice produced a significant 3-fold increase in the mean concentration required to produce a half-maximal relaxing effect (EC(50)) of ACh as compared with control mice. This reflects a weaker sensitivity to ACh of the aortic segments from the apoE-deficient animals. In the second part of the study, the mean EC(50) for ACh after high-fat feeding was found to be 4.4-fold lower in apoE-KO/HuAITg mice than in apoE-KO mice, indicating that the reduced sensitivity to ACh of the thoracic aorta from the apoE-KO mice fed the high-fat diet is improved by the expression of human apoA-I. CONCLUSIONS: The present study demonstrates that the endothelium-dependent arterial relaxation is impaired in apoE-KO mice fed the high-fat diet. The endothelium dysfunction tends to be normalized by human apoA-I expression.
Authors:
V Deckert; G Lizard; N Duverger; A Athias; V Palleau; F Emmanuel; M Moisant; P Gambert; C Lallemant; L Lagrost
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation     Volume:  100     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  1999 Sep 
Date Detail:
Created Date:  1999-10-06     Completed Date:  1999-10-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1230-5     Citation Subset:  AIM; IM    
Affiliation:
Laboratoire de Biochimie des Lipoprotéines - INSERM U498, Hôpital du Bocage, Dijon, France.
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MeSH Terms
Descriptor/Qualifier:
Acetylcholine / pharmacology
Animals
Apolipoprotein A-I / analysis,  physiology*
Apolipoproteins E / deficiency*
Arteriosclerosis / physiopathology
Diet, Atherogenic
Dietary Fats / administration & dosage*
Endothelium, Vascular / physiology*
Female
Humans
Mice
Mice, Inbred C57BL
Mice, Knockout
Nitroprusside / pharmacology
Norepinephrine / pharmacology
Vasodilation / physiology*
Vasodilator Agents / pharmacology
Chemical
Reg. No./Substance:
0/Apolipoprotein A-I; 0/Apolipoproteins E; 0/Dietary Fats; 0/Vasodilator Agents; 15078-28-1/Nitroprusside; 51-41-2/Norepinephrine; 51-84-3/Acetylcholine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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