Document Detail

Diet-induced occlusive coronary atherosclerosis, myocardial infarction, cardiac dysfunction, and premature death in scavenger receptor class B type I-deficient, hypomorphic apolipoprotein ER61 mice.
MedLine Citation:
PMID:  15967843     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Normal chow (low fat)-fed mice deficient in both the HDL receptor SR-BI and apolipoprotein E (SR-BI/apoE dKO) provide a distinctive model of coronary heart disease (CHD). They exhibit early-onset hypercholesterolemia characterized by unesterified cholesterol-rich abnormal lipoproteins (lamellar/vesicular and stacked discoidal particles), occlusive coronary atherosclerosis, spontaneous myocardial infarction, cardiac dysfunction, and premature death ( approximately 6 weeks of age). Mice in which similar features of CHD could be induced with a lipid-rich diet would represent a powerful tool to study CHD. METHODS AND RESULTS: To generate a diet-inducible model of CHD, we bred SR-BI-deficient (SR-BI KO) mice with hypomorphic apolipoprotein E mice (ApoeR61(h/h)) that express reduced levels of an apoE4-like murine apoE isoform and exhibit diet-induced hypercholesterolemia. When fed a normal chow diet, SR-BI KO/ApoeR61(h/h) mice did not exhibit early-onset atherosclerosis or CHD; the low expression level of the apoE4-like murine apoE was atheroprotective and cardioprotective. However, when fed an atherogenic diet rich in fat, cholesterol, and cholate, they rapidly developed hypercholesterolemia, atherosclerosis, and CHD, a response strikingly similar to that of SR-BI/apoE dKO mice fed a chow diet, and they died 32+/-6 days (50% mortality) after initiation of the high-fat feeding. CONCLUSIONS: The SR-BI KO/ApoeR61(h/h) mouse is a new model of diet-induced occlusive coronary atherosclerosis and CHD (myocardial infarction, cardiac dysfunction and premature death), allowing control of the age of onset, duration, severity, and possibly regression of disease. Thus, SR-BI KO/ApoeR61(h/h) mice have the potential to contribute to our understanding of CHD and its prevention and treatment.
Songwen Zhang; Michael H Picard; Eliza Vasile; Yu Zhu; Robert L Raffai; Karl H Weisgraber; Monty Krieger
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2005-06-20
Journal Detail:
Title:  Circulation     Volume:  111     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2005 Jun 
Date Detail:
Created Date:  2005-06-28     Completed Date:  2006-02-03     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3457-64     Citation Subset:  AIM; IM    
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
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MeSH Terms
Apolipoproteins E / physiology*
Cardiomegaly / pathology
Coronary Artery Disease / etiology
Diet, Atherogenic*
Disease Models, Animal*
Heart Diseases / etiology*,  mortality,  pathology,  physiopathology
Heart Failure / etiology
Hypercholesterolemia / etiology
Lipids / blood
Mice, Knockout
Myocardial Infarction / etiology
Scavenger Receptors, Class B / deficiency*
Grant Support
Reg. No./Substance:
0/Apolipoproteins E; 0/Lipids; 0/SCARB1 protein, human; 0/Scavenger Receptors, Class B; 0/apolipoprotein E (Arg61), mouse
Comment In:
Circulation. 2005 Jun 28;111(25):3349-51   [PMID:  15983260 ]

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