| siRNA induced liver ApoB knockdown lowers serum LDL-cholesterol in a mouse model with human-like serum lipids. | |
| | |
MedLine Citation:
|
PMID: 21398511 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Increased serum apoB and associated low density lipoprotein cholesterol (LDL) levels are well correlated with an increased risk of coronary disease. Apo E-/- and LDLr -/- mice have been extensively used for studies of coronary atherosclerosis. These animals show atherosclerotic lesions similar to those in humans, but their serum lipids are low in apoB containing LDL particles. We describe the development of a new mouse model with a human-like lipid profile. Ldlr+/- CETP+/- hemizygous mice carry a single copy of the human CETP transgene and a single copy of a LDL receptor mutation. To evaluate the apoB pathways in this mouse model, we used novel siRNAs formulated in lipid nanoparticles (LNPs). ApoB siRNAs induced up to 95% reduction of liver ApoB mRNA and serum apoB protein, and a significant lowering of serum LDL in Ldlr+/- CETP+/- mice. ApoB targeting is specific, dose dependent and shows lipid lowering effects for over three weeks. Although specific TGs were affected by ApoB KD, and the total plasma lipid levels were decreased by 70%, the overall lipid distribution did not change. Results presented here demonstrate a new mouse model for investigating additional targets within the ApoB pathways using the siRNA modality. |
| | |
Authors:
|
Marija Tadin-Strapps; Laurence B Peterson; Anne-Marie Cumiskey; Raymond L Rosa; Vivienne Halili Mendoza; Jose Castro-Perez; Oscar Puig; Liwen Zhang; Walter R Strapps; Satyasri Yendluri; Lori Andrews; Victoria Pickering; Julie Rice; Lily Luo; Samnang Tep; Brandon Ason; Elizabeth Polizzi Sommers; Alan B Sachs; Steven R Bartz; Jenny Tian; Jayne Chin; Brian K Hubbard; Kenny K Wong; Lyndon J Mitnaul |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-3-11 |
Journal Detail:
|
Title: Journal of lipid research Volume: - ISSN: 0022-2275 ISO Abbreviation: - Publication Date: 2011 Mar |
Date Detail:
|
Created Date: 2011-3-14 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0376606 Medline TA: J Lipid Res Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Merck & Co. Inc. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Orthologues of the anaphase-promoting complex/cyclosome coactivators Cdc20p and Cdh1p are important ...
Next Document: Echocardiographic evaluation of hemodynamics in patients with decompensated systolic heart failure.