title: Probucol inhibits MMP-9 expression through regulating miR-497 in HUVECs and apoE knockout mice.
abstract: OBJECTIVE
  This study investigated the molecular mechanisms underlying the inhibition of MMP-9 expression by probucol, which is widely used for atherosclerotic prevention, in cultured human umbilical vein endothelial cells (HUVECs) and apoE knockout mice.
  
  
  METHODS
  We used three target scan algorithms and observed that microRNA (miR)-497 targeted MEK1, a member of the MAPK/ERK signaling involved in regulating MMP-9 expression. HUVECs were treated with TNFα, and apoE knockout mice were fed a high-fat/high-cholesterol diet with or without probucol pretreatment. We focused on the association between miR-497 and MAPK/ERK signaling and MMP-9 expression.
  
  
  RESULTS
  First, miR-497 expression was significantly higher in the probucol-treated HUVECs and apoE knockout mice compared with non-probucol-treated HUVECs and apoE knockout mice (both p<0.05). Second, MAPK/ERK signaling and MMP-9 levels were downregulated in probucol-treated HUVECs that were treated with TNFα (p<0.01), while MAPK/ERK signaling and MMP-9 levels were upregulated after suppression of miR-497 (p<0.01). Third, probucol increased miR-497 expression levels in the aortas of apoE knockout mice (p<0.05) while decreasing the levels of serum lipids and plaque areas (p<0.05), which decreased the MAPK/ERK signaling and MMP-9 levels (p<0.05).
  
  
  CONCLUSIONS
  Probucol inhibits MMP-9 expression through regulating miR-497 in HUVECs and apoE knockout mice.
authors.affiliation: Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Tianjin Institute of Cardiology, Department of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People's Republic of China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Wang
authors.affiliation: Department of Endocrinology and Metabolism, General Hospital of Tianjin Medical University, Tianjin 300052, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Tianjin Institute of Cardiology, Department of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People's Republic of China.
authors.forename: Xing-Hua
authors.initials: XH
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Tianjin Institute of Cardiology, Department of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People's Republic of China.
authors.forename: Meng
authors.initials: M
authors.lastname: Yuan
authors.affiliation: Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Tianjin Institute of Cardiology, Department of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People's Republic of China. Electronic address: tjcardiol@126.com.
authors.forename: Guang-Ping
authors.initials: GP
authors.lastname: Li
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D001057:Apolipoproteins E / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008055:Lipids / Q000097:blood; D020935:MAP Kinase Signaling System; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D011341:Probucol / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000924:Anticholesteremic Agents; D001057:Apolipoproteins E; D008055:Lipids; C559640:MIRN497 microRNA, human; D035683:MicroRNAs; C550139:mirn497 microRNA, mouse; D020780:Matrix Metalloproteinase 9; D011341:Probucol
keywords: Matrix metalloproteinases; MicroRNAs; Probucol