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Proatherogenic macrophage activities are targeted by the flavonoid quercetin.
MedLine Citation:
PMID:  22869926     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Many studies have demonstrated that the flavonoid quercetin protects against cardiovascular disease (CVD) and related risk factors. Atherosclerosis, the underlying cause of CVD, is also attenuated by oral quercetin administration in animal models. Although macrophages are key players during fatty streak formation and plaque progression and aggravation, little is known about the effects of quercetin on atherogenic macrophages. Here, we report that primary bone marrow-derived macrophages internalized less oxidized low-density lipoprotein (oxLDL) and accumulated less intracellular cholesterol in the presence of quercetin. This reduction of foam cell formation correlated with reduced surface expression of the oxLDL receptor CD36. Quercetin also targeted the LPS-dependent, oxLDL-independent pathway of lipid droplet formation in macrophages. In oxLDL-stimulated macrophages, quercetin inhibited reactive oxygen species production and IL-6 secretion. In a system that evaluated cholesterol crystal-induced IL-1β secretion via NLRP3 inflammasome activation, quercetin also exhibited an inhibitory effect. Dyslipidemic ApoE-deficient mice chronically treated with intraperitoneal quercetin injections had smaller atheromatous lesions, reduced lipid deposition and less macrophage and T cell inflammatory infiltrate in the aortic roots than vehicle-treated animals. Serum levels of total cholesterol and the lipid peroxidation product malondialdehyde (MDA) were also reduced in these mice. Our results demonstrate that quercetin interferes with both key proatherogenic activities of macrophages, namely foam cell formation and prooxidant/proinflammatory responses, and these effects may explain the atheroprotective properties of this common flavonoid.
Authors:
Oscar J Lara-Guzman; Jorge H Tabares-Guevara; Yudy M Leon-Varela; Rafael M Alvarez; Julian A Londono-Londono; Miguel Roldan; Jelver A Sierra; Jose R Ramirez-Pineda
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-6
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  -     ISSN:  1521-0103     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1 Universidad de Antioquia;
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