title: The roles of p62/SQSTM1 on regulation of matrix metalloproteinase-9 gene expression in response to oxLDL in atherosclerosis.
abstract: OBJECTIVE
  Matrix metalloproteinase-9 (MMP-9) plays an important role in the remodeling of the extracellular matrix in atherosclerosis plaques. Autophagy protects macrophages against the processes of vascular disease. Our research explores how autophagy plays roles in macrophages to secret MMP-9.
  
  
  RESULTS
  In response to increased doses of oxLDL or CQ we monitored the autophagic flux. Our results revealed that oxLDL was dynamically associated with autophagy and 100 μg/ml oxLDL blocked autophagic flux in THP-1 cells. Moreover p62/SQSTM1 knocking down and CQ respectively inhibited and increased MMP-9 transcriptional expression. These effects were mediated by inhibition of NF-κB.
  
  
  CONCLUSIONS
  Abundant oxLDL blocked autophagic flux resulting in the aggregation of p62/SQSTM1. Then p62/SQSTM1 was involved in gene expression of MMP-9 via NF-κB-dependent signaling, and thus featuring novel plaque vulnerability properties of the atherosclerotic plaque. Understanding the mechanism that selectively modulates p62/SQSTM1 will provide a novel strategy for anti-atherogenesis.
authors.affiliation: Laboratory Diagnostics Department, The Haerbin Medical University, 150001, China. Electronic address: zhoufeng_hyd@163.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Laboratory Diagnostics Department, The Haerbin Medical University, 150001, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Laboratory Diagnostics Department, The Haerbin Medical University, 150001, China.
authors.forename: Hao-feng
authors.initials: HF
authors.lastname: Ning
authors.affiliation: Laboratory Diagnostics Department, The Haerbin Medical University, 150001, China.
authors.forename: Xiao-chen
authors.initials: XC
authors.lastname: Yu
authors.affiliation: Laboratory Diagnostics Department, The First Clinic Hospital Affiliated to Haerbin Medical University, 150001, China. Electronic address: gxr0451@sina.com.
authors.forename: Xiu-ru
authors.initials: XR
authors.lastname: Guan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D001343:Autophagy / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D008077:Lipoproteins, LDL / Q000008:administration & dosage*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D000071456:Sequestosome-1 Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008077:Lipoproteins, LDL; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; C099252:oxidized low density lipoprotein; D020780:Matrix Metalloproteinase 9
keywords: Atherosclerosis; Autophagy; Macrophage; Matrix metalloproteinase-9 (MMP-9); oxLDL; p62/SQSTM1