Document Detail


Anti-inflammatory salicylate beneficially modulates pre-existing atherosclerosis through quenching of NF-κB activity and lowering of cholesterol.
MedLine Citation:
PMID:  20926077     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
OBJECTIVE: Inflammation plays an important role in all stages of atherosclerosis, but little is known about the therapeutic effects of quenching inflammation in already existing atherosclerotic lesions. Putative beneficial effects of salicylate, an inhibitor of NF-κB activation, were studied in mice with established lesions.
METHODS: ApoE*3-Leiden mice received a high-cholesterol diet (HC) to establish atherosclerotic lesions. Reference mice (REF) were sacrificed to determine the lesion area at the start of two interventions. In one intervention group HC diet feeding was continued, but the diet contained salicylate (HC+SAL). As salicylate not only quenches inflammation but also reduces plasma cholesterol, a second intervention group was fed a low-cholesterol diet (LC) resulting in cholesterol levels comparable to HC+SAL. The effects of these interventions on lesion area and composition were assessed after 8 and 16 weeks.
RESULTS: HC+SAL markedly reduced hepatic NF-κB activity compared to REF, and was significantly more effective than LC diet feeding. HC+SAL and LC also quenched aortic NF-κB activity. While continuing HC diet typically further increases total lesion area, 16 weeks of intervention with HC+SAL and LC halted further disease progression and resulted in lesion sizes comparable to that of REF. At the same time, lesion composition was significantly improved, particularly with salicylate. Strikingly, HC+SAL resulted in a lower lesional macrophage content and a greater plaque stability index (ratio of collagen to macrophage area) than LC.
CONCLUSION: Anti-inflammatory salicylate reduces atherosclerotic macrophage content and increases lesion stability of pre-existing plaques through quenching of NF-κB activity and reducing plasma cholesterol.
Authors:
Jitske de Vries-van der Weij; Karin Toet; Susanne Zadelaar; Peter Y Wielinga; Robert Kleemann; Patrick C N Rensen; Teake Kooistra
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-21
Journal Detail:
Title:  Atherosclerosis     Volume:  213     ISSN:  1879-1484     ISO Abbreviation:  Atherosclerosis     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0242543     Medline TA:  Atherosclerosis     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  241-6     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
The Netherlands Organization for Applied Scientific Research (TNO), Biosciences, Gaubius Laboratory, P.O. Box 2215, 2301 CE Leiden, The Netherlands.
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