Document Detail

ApoE suppresses atherosclerosis by reducing lipid accumulation in circulating monocytes and the expression of inflammatory molecules on monocytes and vascular endothelium.
MedLine Citation:
PMID:  22053073     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: We investigated atheroprotective properties of apolipoprotein (apo) E beyond its ability to lower plasma cholesterol. We hypothesized that apoE reduces atherosclerosis by decreasing lipid accumulation in circulating monocytes and the inflammatory state of monocytes and the vascular endothelium.
METHODS AND RESULTS: We developed mice with spontaneous hyperlipidemia with and without plasma apoE. Hypomorphic apoE mice deficient in low-density lipoprotein receptor (Apoe(h/h)Ldlr(-/-)) were compared to Apoe(-/-)Ldlr(-/-) mice. Despite 4-fold more plasma apoE than WT mice, Apoe(h/h)Ldlr(-/-) mice displayed similar plasma cholesterol as Apoe(-/-) Ldlr(-/-) mice but developed 4-fold less atherosclerotic lesions by 5 months of age. The aortic arch of Apoe(h/h)Ldlr(-/-) mice showed decreased endothelial expression of ICAM-1, PECAM-1, and JAM-A. In addition, Apoe(h/h)Ldlr(-/-) mice had less circulating leukocytes and proinflammatory Ly6C(high) monocytes. These monocytes had decreased neutral lipid content and reduced surface expression of ICAM-1, VLA-4, and L-Selectin. Apoe(h/h)Ldlr(-/-) mice displayed increased levels of apoA1-rich HDL that were potent in promoting cellular cholesterol efflux.
CONCLUSIONS: Our findings suggest that apoE reduces atherosclerosis in the setting of hyperlipidemia by increasing plasma apoA1-HDL that likely contribute to reduce intracellular lipid accumulation and thereby the activation of circulating leukocytes and the vascular endothelium.
Nathalie Gaudreault; Nikit Kumar; Jessica M Posada; Kyle B Stephens; Nabora Soledad Reyes de Mochel; Delphine Eberlé; Victor R Olivas; Roy Y Kim; Matthew J Harms; Sean Johnson; Louis M Messina; Joseph H Rapp; Robert L Raffai
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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, Non-P.H.S.     Date:  2011-11-03
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  32     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-01-19     Completed Date:  2012-03-13     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  264-72     Citation Subset:  IM    
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MeSH Terms
Antigens, CD31 / metabolism
Apolipoproteins E / deficiency,  metabolism*
Atherosclerosis / metabolism*,  prevention & control*
Cell Adhesion Molecules / metabolism
Cholesterol / metabolism
Disease Models, Animal
Endothelium, Vascular / metabolism*
Inflammation Mediators / metabolism*
Integrin alpha4beta1 / metabolism
Intercellular Adhesion Molecule-1 / metabolism
L-Selectin / metabolism
Lipid Metabolism*
Mice, Inbred C57BL
Mice, Knockout
Monocytes / metabolism*
Receptors, Cell Surface / metabolism
Receptors, LDL / deficiency,  metabolism
Grant Support
Reg. No./Substance:
0/Antigens, CD31; 0/Apolipoproteins E; 0/Cell Adhesion Molecules; 0/F11r protein, mouse; 0/Inflammation Mediators; 0/Integrin alpha4beta1; 0/Receptors, Cell Surface; 0/Receptors, LDL; 126547-89-5/Intercellular Adhesion Molecule-1; 126880-86-2/L-Selectin; 97C5T2UQ7J/Cholesterol

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