Title
Anti-inflammatory salicylate beneficially modulates pre-existing atherosclerosis through quenching of NF-κB activity and lowering of cholesterol
Author
de Vries-van der Weij, J.
Toet, K.
Zadelaar, A.S.M.
Wielinga, P.Y.
Kleemann, R.
Rensen, P.C.N.
Kooistra, T.
TNO Kwaliteit van Leven
Publication year
2010
Abstract
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. © 2010 Elsevier Ireland Ltd.
Subject
Health
Biomedical Research
Anti-inflammatory treatment
Established lesions
Inflammation
Mouse model of atherosclerosis
NF-κB
On-top of statin treatment
Reduce further progression of atherosclerosis
Serum amyloid A (SAA)
Statin
hydroxymethylglutaryl coenzyme A reductase inhibitor
immunoglobulin enhancer binding protein
salicylic acid
serum amyloid A
STAT3 protein
animal experiment
animal model
antiinflammatory activity
aorta
article
atherosclerosis
atherosclerotic plaque
cholesterol blood level
cholesterol diet
controlled study
disease course
drug effect
female
histology
hypercholesterolemia
inflammation
liver
low fat diet
macrophage
mouse
nonhuman
priority journal
risk factor
treatment outcome
To reference this document use:
http://resolver.tudelft.nl/uuid:cfd6d3ae-ed1d-4fb6-8fec-8a189fa251b1
TNO identifier
425146
ISSN
0021-9150
Source
Atherosclerosis, 213 (1), 241-246
Document type
article