Document Detail

Accelerated atherosclerosis, aortic aneurysm formation, and ischemic heart disease in apolipoprotein E/endothelial nitric oxide synthase double-knockout mice.
MedLine Citation:
PMID:  11468208     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: To test whether deficiency in endothelial nitric oxide synthase (eNOS) affects atherosclerosis development, we compared lesion formation in apolipoprotein E (apoE)/eNOS-double knockout (DKO) and apoE-knockout (KO) control animals. METHODS AND RESULTS: After 16 weeks of "Western-type" diet, apoE/eNOS-DKO males and females showed significant increases in lesion area of 93.6% and 59.2% compared with apoE-KO mice. All apoE/eNOS-DKO animals studied developed peripheral coronary arteriosclerosis, associated with perivascular and myocardial fibrosis, whereas none of the apoE-KO mice did. Transthoracic echocardiography showed a significantly increased left ventricular wall thickness and decreased fractional shortening in DKO animals. Mean arterial pressure was increased in DKO mice and was comparable in degree to eNOS-KO animals. Male DKO animals developed atherosclerotic abdominal aneurysms and aortic dissection. CONCLUSIONS: eNOS deficiency increases atherosclerosis in Western-type diet-fed apoE-KO animals and introduces coronary disease and an array of cardiovascular complications, including spontaneous aortic aneurysm and dissection. This phenotype constitutes the first murine model to demonstrate distal coronary arteriosclerosis associated with evidence of myocardial ischemia, infarction, and heart failure. Hypertrophy and reduced left ventricular function cannot be explained by increased blood pressure alone, because eNOS-KO animals do not develop these complications.
P J Kuhlencordt; R Gyurko; F Han; M Scherrer-Crosbie; T H Aretz; R Hajjar; M H Picard; P L Huang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation     Volume:  104     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2001 Jul 
Date Detail:
Created Date:  2001-07-24     Completed Date:  2001-09-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  448-54     Citation Subset:  AIM; IM    
Cardiovascular Research Center, Cardiology Division, Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.
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MeSH Terms
Aorta, Abdominal / metabolism,  pathology
Aorta, Thoracic / metabolism,  pathology
Aortic Aneurysm / genetics,  pathology,  physiopathology
Apolipoproteins / genetics*
Arteriosclerosis / genetics,  pathology,  physiopathology
Blood Pressure / genetics,  physiology
Cardiovascular Diseases / genetics,  pathology*,  physiopathology
Heart Rate / genetics,  physiology
Lipid Metabolism
Lipids / blood
Mice, Inbred C57BL
Mice, Knockout
Myocardial Ischemia / genetics,  pathology,  physiopathology
Nitric Oxide Synthase / genetics*
Nitric Oxide Synthase Type II
Nitric Oxide Synthase Type III
Reg. No./Substance:
0/Apolipoproteins; 0/Lipids; EC Oxide Synthase; EC Oxide Synthase Type II; EC Oxide Synthase Type III; EC protein, mouse

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