Zymosan-mediated inflammation impairs in vivo reverse cholesterol transport

Abstract

Infl ammation has been proposed to impair HDL function and reverse cholesterol transport (RCT). We investigated the effects of inflammation mediated by zymosan, a yeast glucan, on multiple steps along the RCT pathway in vivo and ex vivo. Acute inflammation with 70 mg/kg zymosan impaired RCT to plasma, liver, and feces similarly by 17-22% ( P < 0.05), with no additional block at the liver. Hepatic gene expression further demonstrated no change in ABCG5, BCB4, and ABCB11 expression but a decline in ABCG8 mRNA (32% P < 0.05). Plasma from zymosan-treated mice had a 21% decrease in cholesterol acceptor ability ( P < 0.01) and a 35% decrease in ABCA1-specfi c effl ux capacity ( P < 0.01) in vitro. Zymosan treatment also decreased HDL levels and led to HDL remodeling with increased incorporation of serum amyloid A. In addition, cholesterol effl ux from cultured macrophages declined with zymosan treatment in a dose dependant manner. Taken together, our results suggest that zymosan impairs in vivo RCT primarily by decreasing macrophage-derived cholesterol entering the plasma, with minimal additional blocks downstream. Our study supports the notion that RCT impairment is one of the mechanisms for the increased atherosclerotic burden observed in infl ammatory conditions. Copyright © 2011 by the American Society for Biochemistry and Molecular Biology, Inc.