title: 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.affiliation: The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361005 China.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiang-An South Road, Xiamen, Fujian 360112 China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Medical College, Xiamen University, Xiamen, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Su
authors.affiliation: The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361005 China.
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Huang
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong 250012 China.
authors.forename: Yuemao
authors.initials: Y
authors.lastname: Shen
authors.affiliation: The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361005 China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Li
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiang-An South Road, Xiamen, Fujian 360112 China.
authors.forename: Chundong
authors.initials: C
authors.lastname: Yu
keywords: Atherosclerosis; Foam cell; Macrophage; Mycoepoxydiene; ox-LDL