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

Abstract

BACKGROUND:

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. 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.

RESULTS:

Our 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.

CONCLUSIONS:

Our 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.

• Authors: Xiaochun Xia, Yang Li, Qiang Su, Zhengrong Huang, Yuemao Shen, Weihua Li, Chundong Yu
• Journal: Cell & bioscience (Cell Biosci) Vol. 5 Pg. 23 ( 2015) ISSN: 2045-3701 [Print] England
• PMID: 26045945 (Publication Type: Journal Article)