Document Detail

Fenofibrate reduces atherogenesis in ApoE*3Leiden mice: evidence for multiple antiatherogenic effects besides lowering plasma cholesterol.
MedLine Citation:
PMID:  16873727     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: To demonstrate, quantify, and mechanistically dissect antiatherosclerotic effects of fenofibrate besides lowering plasma cholesterol per se. METHODS AND RESULTS: ApoE*3Leiden transgenic mice received either a high-cholesterol diet (HC) or HC containing fenofibrate (HC+FF) resulting in 52% plasma cholesterol-lowering. In a separate low-cholesterol diet (LC) control group, plasma cholesterol was adjusted to the level achieved in the HC+FF group. Low plasma cholesterol alone (assessed in LC) resulted in reduced atherosclerosis (lesion area, number and severity) and moderately decreased plasma serum amyloid-A (SAA) concentrations. Compared with LC, fenofibrate additively reduced lesion area, number and severity, and the total aortic plaque load. This additional effect in HC+FF was paralleled by an extra reduction of aortic inflammation (macrophage content; monocyte adhesion; intercellular adhesion molecule-1 [ICAM-1], soluble vascular cell adhesion molecule-1, granulocyte-macrophage colony-stimulating factor (GM-CSF), MCP-1, and NF-kappaB expression), systemic inflammation (plasma SAA and fibrinogen levels), and by an upregulation of plasma apoE levels. Also, enhanced expression of ABC-A1 and SR-B1 in aortic macrophages may contribute to the antiatherosclerotic effect of fenofibrate by promoting cholesterol efflux. CONCLUSIONS: Fenofibrate reduces atherosclerosis more than can be explained by lowering total plasma cholesterol per se. Impaired recruitment of monocytes/macrophages, reduced vascular and systemic inflammation, and stimulation of cholesterol efflux may all contribute to these beneficial effect of fenofibrate.
T Kooistra; L Verschuren; J de Vries-van der Weij; W Koenig; K Toet; H M G Princen; R Kleemann
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-07-27
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  26     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-09-22     Completed Date:  2006-10-20     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2322-30     Citation Subset:  IM    
Gaubius Laboratory, TNO-Pharma, P.O.Box 2215, 2301 CE Leiden, The Netherlands.
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MeSH Terms
Antilipemic Agents / pharmacology*
Aorta / pathology
Aortic Valve / pathology
Apolipoprotein E3
Apolipoproteins E / genetics,  metabolism*
Atherosclerosis / blood*,  pathology*
Cholesterol / blood*
Inflammation / pathology
Lipids / blood
Lipoproteins / blood
Mice, Transgenic
Procetofen / pharmacology*
Reg. No./Substance:
0/Antilipemic Agents; 0/Apolipoprotein E3; 0/Apolipoproteins E; 0/Lipids; 0/Lipoproteins; 0/apolipoprotein E3 (Leidein); 49562-28-9/Procetofen; 57-88-5/Cholesterol

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