Exp Mol Med.  2009 Mar;41(3):171-179. 10.3858/emm.2009.41.3.020.

Resveratrol inhibits foam cell formation via NADPH oxidase 1-mediated reactive oxygen species and monocyte chemotactic protein-1

• Park DW
• Baek K
• Kim JR
• Lee JJ
• Ryu SH
• Chin BR
• Baek SH

• KMID: 1123464
• DOI: http://doi.org/10.3858/emm.2009.41.3.020

Abstract

Resveratrol is a polyphenolic compound in red wine that has anti-oxidant and cardioprotective effects in animal models. Reactive oxygen species (ROS) and monocyte chemotactic protein-1 (MCP-1) play key roles in foam cell formation and atherosclerosis. We studied LPS-mediated foam cell formation and the effect of resveratrol. Resveratrol pretreatment strongly suppressed LPS-induced foam cell formation. To determine if resveratrol affected the expression of genes that control ROS generation in macrophages, NADPH oxidase 1 (Nox1) was measured. Resveratrol treatment of macrophages inhibited LPS-induced Nox1 expression as well as ROS generation, and also suppressed LPS-induced MCP-1 mRNA and protein expression. We investigated the upstream targets of Nox1 and MCP-1 expression and found that Akt-forkhead transcription factors of the O class (FoxO3a) is an important signaling pathway that regulates both genes. These inhibitory effects of resveratrol on Nox1 expression and MCP-1 production may target to the Akt and FoxO3a signaling pathways.

Keyword

atherosclerosis; CCL2 protein; foam cells; FoxO3a protein; NADPH oxidase 1; reactive oxygen species; resveratrol

MeSH Terms

Antioxidants/*pharmacology
Cells, Cultured
Chemokine CCL2/genetics/*metabolism
Enzyme Activation/drug effects
Foam Cells/*drug effects/physiology
Forkhead Transcription Factors/metabolism
Humans
Lipopolysaccharides/pharmacology
NADH, NADPH Oxidoreductases/genetics/*metabolism
Proto-Oncogene Proteins c-akt/metabolism
RNA, Messenger/metabolism
Reactive Oxygen Species/*metabolism
Signal Transduction
Stilbenes/*pharmacology