Inhibitory effects of Mycoepoxydiene on macrophage foam cell formation and atherosclerosis in ApoE-deficient mice

Xiaochun Xia,Yuemao Shen,Chundong Yu,Weihua Li,Qiang Su,Zhengrong Huang,Yang Li

doi:10.1186/s13578-015-0017-y

Abstract

BackgroundMycoepoxydiene (MED) is a polyketide that can be isolated from a marine fungus and is associated with various activities, including antitumor and anti-inflammatory functions. However, its effects on atherosclerosis remain unknown. Macrophage-derived foam cells play crucial roles in the initiation and progression of atherosclerotic plaques. In this study, we investigated the effects of MED on oxidized low-density lipoprotein (ox-LDL)-induced macrophage foam cell formation and activation, and on high fat diet (HFD)-induced atherosclerosis in ApoE-deficient (ApoE−/−) mice.ResultsOur findings show that MED could significantly inhibit ox-LDL-induced macrophage foam cell formation and suppress the expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), which is a receptor for ox-LDL. Additionally, MED could significantly inhibit the secretion of proinflammatory cytokines, such as tumor necrosis factor (TNF-α), interleukin (IL)-6, and IL-1β. Mechanistically, MED inhibited NF-κB activation by blocking IκB-α degradation and reducing NF-κB DNA binding activity. Moreover, MED dramatically reduced the occurrence of HFD-induced atherosclerotic lesions in ApoE−/− mice.ConclusionsOur study shows that MED can inhibit macrophage foam cell formation and activation by inhibiting NF-κB activation, thereby protecting ApoE−/− mice from HFD-induced atherosclerosis. Our findings suggest that MED might be a potential lead compound for the development of antiatherosclerotic therapeutics.Electronic supplementary materialThe online version of this article (doi:10.1186/s13578-015-0017-y) contains supplementary material, which is available to authorized users.

Highlights

Mycoepoxydiene (MED) is a polyketide that can be isolated from a marine fungus and is associated with various activities, including antitumor and anti-inflammatory functions
MED significantly suppresses macrophage foam cell formation Foam cells are pathogenic cells in atherosclerosis that are derived from monocytes/macrophages and vascular smooth muscle cells
To explore whether MED affected foam cell formation, RAW264.7 cells were treated with oxidized low-density lipoprotein (ox-low-density lipoprotein (LDL)) in the absence or presence of different concentrations of MED for 24 h and were stained with Oil-red O solution

Summary

Introduction

Mycoepoxydiene (MED) is a polyketide that can be isolated from a marine fungus and is associated with various activities, including antitumor and anti-inflammatory functions. Macrophage-derived foam cells play crucial roles in the initiation and progression of atherosclerotic plaques. We investigated the effects of MED on oxidized low-density lipoprotein (ox-LDL)-induced macrophage foam cell formation and activation, and on high fat diet (HFD)-induced atherosclerosis in ApoE-deficient (ApoE−/−) mice. Studies have shown that inflammation plays a critical role in all stages, from initiation through progression, and drives the thrombotic complications of atherosclerosis. Ox-LDL plays a critical role in triggering proinflammatory and pro-oxidant events in the initiation, propagation, and LOX-1, which is a lectin-like receptor for ox-LDL in endothelial cells, smooth muscle cells, and macrophages [7,8,9], plays important roles in atherosclerosis development [10]. LOX-1 can be dynamically up-regulated by various proinflammatory, pro-oxidative, and mechanical stimuli [14,15,16].

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