| Cholesterol efflux potential and antiinflammatory properties of high-density lipoprotein after treatment with niacin or anacetrapib. | |
| | |
MedLine Citation:
|
PMID: 20448206 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
OBJECTIVE: To examine the effects of treatments with niacin or anacetrapib (an inhibitor of cholesteryl ester transfer protein) on the ability of high-density lipoprotein (HDL) to promote net cholesterol efflux and reduce toll-like receptor-mediated inflammation in macrophages. METHODS AND RESULTS: A total of 18 patients received niacin, 2 g/d, for 4 weeks; 20 patients received anacetrapib, 300 mg/d, for 8 weeks; and 2 groups (n=4 and n=5 patients) received placebo. HDL samples were isolated by polyethylene glycol precipitation or ultracentrifugation, tested for the ability to promote cholesterol efflux in cholesterol-loaded THP-I or mouse peritoneal macrophages, or used to pretreat macrophages, followed by lipopolysaccharide exposure. HDL cholesterol levels were increased by 30% in response to niacin and by approximately 100% in response to anacetrapib. Niacin treatment increased HDL-mediated net cholesterol efflux from foam cells, primarily by increasing HDL concentration, whereas anacetrapib treatment increased cholesterol efflux by both increasing HDL concentration and causing increased efflux at matched HDL concentrations. The increased efflux potential of anacetrapib-HDL was more prominent at higher HDL cholesterol concentrations (>12 microg/mL), which was associated with an increased content of lecithin-cholesterol acyltransferase (LCAT) and apolipoprotein E and completely dependent on the expression of ATP binding cassette transporters (ABCA1 and ABCG1). Potent antiinflammatory effects of HDL were observed at low HDL concentrations (3 to 20 microg/mL) and were partly dependent on the expression of ABCA1 and ABCG1. All HDL preparations showed similar antiinflammatory effects, proportionate to the HDL cholesterol concentration. CONCLUSIONS: Niacin treatment caused a moderate increase in the ability of HDL to promote net cholesterol efflux, whereas inhibition of cholesteryl ester transfer protein via anacetrapib led to a more dramatic increase in association with enhanced particle functionality at higher HDL concentrations. All HDLs exhibited potent ability to suppress macrophage toll-like receptor 4-mediated inflammatory responses, in a process partly dependent on cholesterol efflux via ABCA1 and ABCG1. |
| | |
Authors:
|
Laurent Yvan-Charvet; Jelena Kling; Tamara Pagler; Hongna Li; Brian Hubbard; Tim Fisher; Carl P Sparrow; Andrew K Taggart; Alan R Tall |
Related Documents
:
|
9585166 - Involvement of high density lipoprotein as substrate cholesterol for steroidogenesis by... 2461206 - Modifications of plasma lipids, lipoproteins and apolipoproteins in advanced cancer pat... 6155066 - Artifactual reduction of high-density lipoprotein cholesterol estimates after dextran s... 1613316 - Effects of lovastatin and gemfibrozil on high-density lipoprotein subfraction density a... 19015756 - Lemon polyphenols suppress diet-induced obesity by up-regulation of mrna levels of the ... 3009246 - Comparison between starvation and consumption of a high protein diet: plasma insulin an... |
Publication Detail:
|
Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-05-06 |
Journal Detail:
|
Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 30 ISSN: 1524-4636 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 2010 Jul |
Date Detail:
|
Created Date: 2010-06-17 Completed Date: 2010-07-12 Revised Date: 2011-09-26 |
Medline Journal Info:
|
Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: United States |
Other Details:
|
Languages: eng Pagination: 1430-8 Citation Subset: IM |
Affiliation:
|
Division of Molecular Medicine, Department of Medicine, Columbia University, 630 W 168th St, New York, NY 10032, USA. ly2159@columbia.edu |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
ATP-Binding Cassette Transporters
/
genetics,
metabolism Animals Anti-Inflammatory Agents / adverse effects, therapeutic use* Cells, Cultured Cholesterol / blood* Cholesterol Ester Transfer Proteins / antagonists & inhibitors*, metabolism Cholesterol, HDL / blood* Clinical Trials as Topic Dyslipidemias / blood, drug therapy*, immunology Foam Cells / metabolism Humans Hypolipidemic Agents / adverse effects, therapeutic use* Inflammation / immunology, metabolism, prevention & control* Inflammation Mediators / metabolism Lipoproteins / deficiency, genetics, metabolism Macrophages / immunology, metabolism* Mice Mice, Knockout Niacin / adverse effects, therapeutic use* Oxazolidinones / adverse effects, therapeutic use* Time Factors Toll-Like Receptor 4 / metabolism Treatment Outcome |
| Grant Support | |
ID/Acronym/Agency:
|
HL 22682/HL/NHLBI NIH HHS; R37 HL022682-18/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/ABCG1 protein, mouse; 0/ATP binding cassette transporter 1; 0/ATP-Binding Cassette Transporters; 0/Anti-Inflammatory Agents; 0/CETP protein, human; 0/Cholesterol Ester Transfer Proteins; 0/Cholesterol, HDL; 0/Hypolipidemic Agents; 0/Inflammation Mediators; 0/Lipoproteins; 0/Oxazolidinones; 0/Tlr4 protein, mouse; 0/Toll-Like Receptor 4; 0/anacetrapib; 57-88-5/Cholesterol; 59-67-6/Niacin |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Stroke Therapy in Patients Considering Prothrombin Time and International Normalized Ratio.
Next Document: Glucagon-Like Peptide 1 Prevents Reactive Oxygen Species-Induced Endothelial Cell Senescence Through...