| Molecular etiology of a dominant form of type III hyperlipoproteinemia caused by R142C substitution in apoE4. | |
| | |
MedLine Citation:
|
PMID: 20861163 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
We have used adenovirus-mediated gene transfer in apolipoprotein (apo)E(-/-) mice to elucidate the molecular etiology of a dominant form of type III hyperlipoproteinemia (HLP) caused by the R142C substitution in apoE4. It was found that low doses of adenovirus expressing apoE4 cleared cholesterol, whereas comparable doses of apoE4[R142C] greatly increased plasma cholesterol, triglyceride, and apoE levels, caused accumulation of apoE in VLDL/IDL/LDL region, and promoted the formation of discoidal HDL. Co-expression of apoE4[R142C] with lecithin cholesterol acyltransferase (LCAT) or lipoprotein lipase (LPL) in apoE(-/-) mice partially corrected the apoE4[R142C]-induced dyslipidemia. High doses of C-terminally truncated apoE4[R142C]-202 partially cleared cholesterol in apoE(-/-) mice and promoted formation of discoidal HDL. The findings establish that apoE4[R142C] causes accumulation of apoE in VLDL/IDL/LDL region and affects in vivo the activity of LCAT and LPL, the maturation of HDL, and the clearance of triglyceride-rich lipoproteins. The prevention of apoE4[R142C]-induced dyslipidemia by deletion of the 203-299 residues suggests that, in the full-length protein, the R142C substitution may have altered the conformation of apoE bound to VLDL/IDL/LDL in ways that prevent triglyceride hydrolysis, cholesterol esterification, and receptor-mediated clearance in vivo. |
| | |
Authors:
|
Alexander M Vezeridis; Konstantinos Drosatos; Vassilis I Zannis |
Related Documents
:
|
19703533 - Total panax notoginsenosides prevent atherosclerosis in apolipoprotein e-knockout mice:... 7417373 - Acute effects of the pattern of fat ingestion on plasma high density lipoprotein compon... 20607063 - Hypocholesterolemic effects of curcumin via up-regulation of cholesterol 7a-hydroxylase... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-09-22 |
Journal Detail:
|
Title: Journal of lipid research Volume: 52 ISSN: 0022-2275 ISO Abbreviation: J. Lipid Res. Publication Date: 2011 Jan |
Date Detail:
|
Created Date: 2010-12-14 Completed Date: 2011-06-21 Revised Date: 2012-01-02 |
Medline Journal Info:
|
Nlm Unique ID: 0376606 Medline TA: J Lipid Res Country: United States |
Other Details:
|
Languages: eng Pagination: 45-56 Citation Subset: IM |
Affiliation:
|
Molecular Genetics, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Apolipoprotein E4 / genetics* Cells, Cultured Humans Hyperlipoproteinemia Type III / genetics*, metabolism Mice Mice, Transgenic Microscopy, Electron Mutation Phenotype Phosphatidylcholine-Sterol O-Acyltransferase / genetics, metabolism Triglycerides / blood, metabolism |
| Grant Support | |
ID/Acronym/Agency:
|
HL007969/HL/NHLBI NIH HHS; HL68216/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Apolipoprotein E4; 0/Triglycerides; EC 2.3.1.43/Phosphatidylcholine-Sterol O-Acyltransferase |
| Comments/Corrections | |
Erratum In:
|
J Lipid Res. 2011 Jun;52(6):1303 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Modulating cholesteryl ester transfer protein activity maintains efficient pre-?-HDL formation and i...
Next Document: The ins and outs of cholesterol in the vertebrate retina.