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Cholesterol efflux potential and antiinflammatory properties of high-density lipoprotein after treatment with niacin or anacetrapib

Yvan-Charvet, Laurent ; Kling, Jelena ; Pagler, Tamara ; Li, Hongna ; Hubbard, Brian ; Fisher, Tim ; Sparrow, Carl P ; Taggart, Andrew K ; Tall, Alan R

Arteriosclerosis, thrombosis, and vascular biology, July 2010, Vol.30(7), pp.1430-8 [Peer Reviewed Journal]

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  • Title:
    Cholesterol efflux potential and antiinflammatory properties of high-density lipoprotein after treatment with niacin or anacetrapib
  • Author: Yvan-Charvet, Laurent ; Kling, Jelena ; Pagler, Tamara ; Li, Hongna ; Hubbard, Brian ; Fisher, Tim ; Sparrow, Carl P ; Taggart, Andrew K ; Tall, Alan R
  • Description: 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. 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... 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.
  • Is Part Of: Arteriosclerosis, thrombosis, and vascular biology, July 2010, Vol.30(7), pp.1430-8
  • Identifier: E-ISSN: 1524-4636 ; PMID: 20448206 Version:1 ; DOI: 10.1161/ATVBAHA.110.207142
  • Subjects: Anti-Inflammatory Agents -- Therapeutic Use ; Cholesterol -- Blood ; Cholesterol Ester Transfer Proteins -- Antagonists & Inhibitors ; Cholesterol, HDL -- Blood ; Dyslipidemias -- Drug Therapy ; Hypolipidemic Agents -- Therapeutic Use ; Inflammation -- Prevention & Control ; Macrophages -- Metabolism ; Niacin -- Therapeutic Use ; Oxazolidinones -- Therapeutic Use
  • Language: English

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