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Proatherogenic macrophage activities are targeted by the flavonoid quercetin.

Authors
  • Lara-Guzman, Oscar J
  • Tabares-Guevara, Jorge H
  • Leon-Varela, Yudy M
  • Álvarez, Rafael M
  • Roldan, Miguel
  • Sierra, Jelver A
  • Londoño-Londoño, Julian A
  • Ramirez-Pineda, Jose R
Type
Published Article
Journal
Journal of Pharmacology and Experimental Therapeutics
Publisher
American Society for Pharmacology & Experimental Therapeutics
Publication Date
November 2012
Volume
343
Issue
2
Pages
296–306
Identifiers
DOI: 10.1124/jpet.112.196147
PMID: 22869926
Source
Medline
License
Unknown

Abstract

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 lipopolysaccharide-dependent, oxLDL-independent pathway of lipid droplet formation in macrophages. In oxLDL-stimulated macrophages, quercetin inhibited reactive oxygen species production and interleukin (IL)-6 secretion. In a system that evaluated cholesterol crystal-induced IL-1β secretion via nucleotide-binding domain and leucine-rich repeat containing protein 3 inflammasome activation, quercetin also exhibited an inhibitory effect. Dyslipidemic apolipoprotein E-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 were also reduced in these mice. Our results demonstrate that quercetin interferes with both key proatherogenic activities of macrophages, namely foam cell formation and pro-oxidant/proinflammatory responses, and these effects may explain the atheroprotective properties of this common flavonoid.

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