Document Detail

Angiotensin II-induced hypertension accelerates the development of atherosclerosis in apoE-deficient mice.
MedLine Citation:
PMID:  11157699     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Angiotensin II may contribute to the development and progression of atherosclerotic lesions because of its growth and proinflammatory effects. We sought to determine whether angiotensin II-induced hypertension would augment and accelerate the development of atherosclerotic lesions in apoE-deficient mice. METHODS AND RESULTS: Angiotensin II (0.7 mg x kg(-1) x d(-1) SC) was administered to apoE-deficient mice via osmotic minipumps. The animals were placed on either standard chow or an atherogenic diet. After 8 weeks, the mean atherosclerotic lesion area in the descending thoracic and abdominal aortas of animals on a standard chow diet was 0.4+/-0.1% compared with 5.2+/-1.2% in those animals maintained on an atherogenic diet (P:<0.0001). In angiotensin II-treated animals on standard chow, the mean lesion area was increased to 11.0+/-2.3%, which was further increased to 69.9+/-9.4% (P:<0.0001) in angiotensin II-treated animals on an atherogenic diet. Similar findings were obtained when tissues from the ascending aorta were analyzed. At 8 weeks in mice receiving a standard chow diet, angiotensin II dramatically increased the atherosclerotic lesion area by 840+/-83 microm(2) (P:<0.0001). Animals on a high-fat diet had a similar marked increase in lesion area in response to angiotensin II (217+/-19 microm(2), P:<0.0001). In contrast, when hypertension was induced with norepinephrine, only a modest effect on the atherosclerotic lesion area was observed. CONCLUSIONS: Angiotensin II-induced hypertension specifically increased the development of atherosclerosis in apoE knockout mice. This response was seen in animals receiving either standard chow or an atherogenic diet. These studies demonstrate the profound effect of angiotensin II on the development of atherosclerosis.
D Weiss; J J Kools; W R Taylor
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation     Volume:  103     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2001 Jan 
Date Detail:
Created Date:  2001-02-22     Completed Date:  2001-04-26     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  448-54     Citation Subset:  IM    
Division of Cardiology, Department of Medicine, Atlanta VA Medical Center and Emory University School of Medicine, Atlanta, GA 30322, USA.
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MeSH Terms
Angiotensin II
Aorta / pathology
Apolipoproteins E / deficiency*,  genetics
Arteriosclerosis / etiology*,  pathology
Diet, Atherogenic
Hypertension / chemically induced,  complications*
Mice, Knockout
Grant Support
Reg. No./Substance:
0/Apolipoproteins E; 11128-99-7/Angiotensin II; 51-41-2/Norepinephrine

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