Title
Anti-inflammatory, anti-proliferative and anti-atherosclerotic effects of quercetin in human in vitro and in vivo models
Author
Kleemann, R.
Verschuren, L.
Morrison, M.
Zadelaar, A.S.M.
van Erk, M.J.
Wielinga, P.Y.
Kooistra, T.
Publication year
2011
Abstract
Objective: Polyphenols such as quercetin may exert several beneficial effects, including those resulting from anti-inflammatory activities, but their impact on cardiovascular health is debated. We investigated the effect of quercetin on cardiovascular risk markers including human C-reactive protein (CRP) and on atherosclerosis using transgenic humanized models of cardiovascular disease. Methods: After evaluating its anti-oxidative and anti-inflammatory effects in cultured human cells, quercetin (0.1%, w/w in diet) was given to human CRP transgenic mice, a humanized inflammation model, and ApoE*3Leiden transgenic mice, a humanized atherosclerosis model. Sodium salicylate was used as an anti-inflammatory reference. Results: In cultured human endothelial cells, quercetin protected against H2O2-induced lipid peroxidation and reduced the cytokine-induced cell-surface expression of VCAM-1 and E-selectin. Quercetin also reduced the transcriptional activity of NF?B in human hepatocytes. In human CRP transgenic mice (quercetin plasma concentration: 12.9±1.3µM), quercetin quenched IL1ß-induced CRP expression, as did sodium salicylate. In ApoE*3Leiden mice, quercetin (plasma concentration: 19.3±8.3µM) significantly attenuated atherosclerosis by 40% (sodium salicylate by 86%). Quercetin did not affect atherogenic plasma lipids or lipoproteins but it significantly lowered the circulating inflammatory risk factors SAA and fibrinogen. Combined histological and microarray analysis of aortas revealed that quercetin affected vascular cell proliferation thereby reducing atherosclerotic lesion growth. Quercetin also reduced the gene expression of specific factors implicated in local vascular inflammation including IL-1R, Ccl8, IKK, and STAT3. Conclusion: Quercetin reduces the expression of human CRP and cardiovascular risk factors (SAA, fibrinogen) in mice in vivo. These systemic effects together with local anti-proliferative and anti-inflammatory effects in the aorta may contribute to the attenuation of atherosclerosis. © 2011 Elsevier Ireland Ltd.
Subject
Life
MHR - Metabolic Health Research MSB - Microbiology and Systems Biology
EELS - Earth, Environmental and Life Sciences
Nutrition
Anti-inflammatory
Atherosclerosis
Cholesterol
CRP
Inflammation
Polyphenol
Proliferation
Quercetin
C reactive protein
endothelial leukocyte adhesion molecule 1
fibrinogen
immunoglobulin enhancer binding protein
quercetin
vascular cell adhesion molecule 1
animal experiment
animal model
antiinflammatory activity
article
atherosclerosis
cardiovascular risk
controlled study
drug activity
drug blood level
drug effect
endothelium cell
human
human cell
inflammation
liver cell
male
mouse
nonhuman
priority journal
protein expression
risk factor
transgenic mouse
To reference this document use:
http://resolver.tudelft.nl/uuid:5aa547eb-5fd4-49f4-aec7-185e5670529b
DOI
https://doi.org/10.1016/j.atherosclerosis.2011.04.023
TNO identifier
435998
ISSN
0021-9150
Source
Atherosclerosis, 218 (1), 44-52
Document type
article