title: MicroRNA-21 is a unique signature associated with coronary plaque instability in humans by regulating matrix metalloproteinase-9 via reversion-inducing cysteine-rich protein with Kazal motifs.
abstract: BACKGROUND
  Coronary atherosclerotic unstable plaque is one of the leading causes of cardiovascular death. Macrophage-derived matrix metalloproteinase (MMP) 9 is considered for degrading extracellular matrix and collagen, thereby thinning the fibrous cap in plaques. miR-21 is implicated to play an important role in the progression of atherosclerosis. Nevertheless, miR-21 as the biomarker for coronary atherosclerotic unstable plaque remains unknown. We aimed to investigate the prediction role of miR-21 for unstable plaque by pathway study of miR-21 on MMPs and its inhibitor RECK in macrophages.
  
  
  METHODS
  Expression of miR-21 in macrophages and serum miR-21 as well as MMP-9 was measured in patients with coronary non-calcified plaque, calcified plaque and controls. In vitro experiment was done in human macrophages by over-expressing miR-21 or down-regulating RECK. The regulation of RECK and MMP-9 by miR-21 was evaluated by western blotting and siRNA strategy.
  
  
  RESULTS
  Patients with non-calcified coronary artery lesions had significantly higher miR-21 in macrophages and lower miR-21 serum levels compared to the control and calcified plaque patients. At the same time, the serum levels of MMP-9 were significantly elevated in non-calcified patients. Experiments in vitro indicated that over-expressing miR-21 could induce the expression and secretion of pro-MMP-9 and active-MMP-9 in human macrophages via targeting gene RECK, and knocking down RECK expression by specific siRNA can resemble that of miR-21 over-expression.
  
  
  CONCLUSIONS
  miR-21 might be a biomarker for plaque instability by suppressing target gene RECK to promote the expression and secretion of MMP-9 in macrophages.
authors.affiliation: State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China; Center for Pediatric Cardiac Surgery, Fuwai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Enshi
authors.initials: E
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Xianyun
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: Cong
authors.affiliation: State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China. Electronic address: chenxipumc@hotmail.com.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D020816:Amino Acid Motifs; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics* / Q000473:pathology; D005260:Female; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000235:genetics*; D035683:MicroRNAs / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000235:genetics / Q000473:pathology; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering
chemical_list: D058851:GPI-Linked Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D011506:Proteins; C115460:RECK protein, human; D034741:RNA, Small Interfering; C074370:cysteine-rich protein, mammalian; D020780:Matrix Metalloproteinase 9
keywords: Atherosclerosis; Coronary plaque instability; MMP-9; RECK; miR-21