Document Detail


Hepatic lipase deficiency delays atherosclerosis, myocardial infarction, and cardiac dysfunction and extends lifespan in SR-BI/apolipoprotein E double knockout mice.
MedLine Citation:
PMID:  16397139     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: SR-BI/apolipoprotein (apo) E double knockout (dKO) mice exhibit many features of human coronary heart disease (CHD), including occlusive coronary atherosclerosis, cardiac hypertrophy, myocardial infarctions, and premature death. Here we determined the effects on this pathology of hepatic lipase (HL) deficiency, which has been shown to significantly modulate atherosclerosis. METHOD AND RESULTS: The SR-BI/apoE/HL triple knockout (tKO) mice generated for this study lived significantly longer (37%) than corresponding dKO controls (average lifespans: 63.0+/-0.8 versus 46.0+/-0.3 days), despite their increased plasma cholesterol levels. At 6 weeks of age, compared with dKO mice, tKOs exhibited significantly less aortic root and coronary artery occlusive atherosclerosis, and improved cardiac structure and function. However, by 9 weeks of age the hearts of tKO mice exhibited lipid-rich coronary occlusions, myocardial infarctions, and cardiac dysfunction essentially identical to that of 6-week-old dKO mice. CONCLUSIONS: HL-deficiency delays the onset and/or progression of atherosclerosis via a SR-BI-independent mechanism. Extent of occlusive coronary arterial lesions was more closely associated with cardiac dysfunction and lifespan than the amount of aortic root atherosclerosis, suggesting that these occlusions in dKO mice are responsible for ischemia, myocardial infarctions, and premature death.
Authors:
Sharon L Karackattu; Bernardo Trigatti; Monty Krieger
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-01-05
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  26     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-02-17     Completed Date:  2006-05-24     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  548-54     Citation Subset:  IM    
Affiliation:
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
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MeSH Terms
Descriptor/Qualifier:
Age of Onset
Animals
Aorta / pathology
Apolipoproteins E / genetics
Cardiomegaly / mortality,  pathology,  physiopathology
Coronary Artery Disease / mortality*,  pathology,  physiopathology*
Coronary Vessels / pathology
Electrocardiography
Female
Life Expectancy
Lipase / deficiency,  genetics*,  metabolism
Lipids / blood
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Myocardial Infarction / mortality*,  pathology,  physiopathology*
Myocardial Ischemia / mortality,  pathology,  physiopathology
Scavenger Receptors, Class B / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
HL64737/HL/NHLBI NIH HHS; HL66105/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Apolipoproteins E; 0/Lipids; 0/Scarb1 protein, mouse; 0/Scavenger Receptors, Class B; EC 3.1.1.3/Lipase; EC 3.1.1.3/Lipc protein, mouse

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