title: Distribution of Matrix Metalloproteinases in Human Atherosclerotic Carotid Plaques and Their Production by Smooth Muscle Cells and Macrophage Subsets.
abstract: OBJECTIVE
  In this study, the potential of matrix metalloproteinase (MMP) sense for detection of atherosclerotic plaque instability was explored. Secondly, expression of MMPs by macrophage subtypes and smooth muscle cells (SMCs) was investigated.
  
  
  METHODS
  Twenty-three consecutive plaques removed during carotid endarterectomy were incubated in MMPSense™ 680 and imaged with IVIS® Spectrum. mRNA levels of MMPs, macrophage markers, and SMCs were determined in plaque specimens, and in in vitro differentiated M1 and M2 macrophages.
  
  
  RESULTS
  There was a significant difference between autofluorescence signals and MMPSense signals, both on the intraluminal and extraluminal sides of plaques. MMP-9 and CD68 messenger RNA (mRNA) expression was higher in hot spots, whereas MMP-2 and αSMA expression was higher in cold spots. In vitro M2 macrophages had higher mRNA expression of MMP-1, MMP-9, MMP-12, and TIMP-1 compared to M1 macrophages.
  
  
  CONCLUSIONS
  MMP-9 is most dominantly MMP present in atherosclerotic plaques and is produced by M2 rather than M1 macrophages.
authors.affiliation: Departments of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, PB 30.001, 9700 RB, Groningen, The Netherlands.
authors.forename: Nynke A
authors.initials: NA
authors.lastname: Jager
authors.affiliation: Department of Surgery, Division of Vascular Surgery, University Medical Center Groningen, University of Groningen, Groningen, PB 30.001, 9700 RB, Groningen, The Netherlands.
authors.forename: Bastiaan M
authors.initials: BM
authors.lastname: Wallis de Vries
authors.affiliation: Departments of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, PB 30.001, 9700 RB, Groningen, The Netherlands.
authors.forename: Jan-Luuk
authors.initials: JL
authors.lastname: Hillebrands
authors.affiliation: Department of Surgery, Division of Vascular Surgery, University Medical Center Groningen, University of Groningen, Groningen, PB 30.001, 9700 RB, Groningen, The Netherlands.
authors.forename: Niels J
authors.initials: NJ
authors.lastname: Harlaar
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, PB 30.001, 9700 RB, Groningen, The Netherlands.
authors.forename: René A
authors.initials: RA
authors.lastname: Tio
authors.affiliation: Departments of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, PB 30.001, 9700 RB, Groningen, The Netherlands.
authors.forename: Riemer H J A
authors.initials: RH
authors.lastname: Slart
authors.affiliation: Department of Surgery, Division of Vascular Surgery, University Medical Center Groningen, University of Groningen, Groningen, PB 30.001, 9700 RB, Groningen, The Netherlands.
authors.forename: Gooitzen M
authors.initials: GM
authors.lastname: van Dam
authors.affiliation: Departments of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, PB 30.001, 9700 RB, Groningen, The Netherlands.|Departments of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, PB 30.001, 9700 RB, Groningen, The Netherlands.
authors.forename: Hendrikus H
authors.initials: HH
authors.lastname: Boersma
authors.affiliation: Department of Surgery, Division of Vascular Surgery, University Medical Center Groningen, University of Groningen, Groningen, PB 30.001, 9700 RB, Groningen, The Netherlands. czeebregts@hotmail.com.
authors.forename: Clark J
authors.initials: CJ
authors.lastname: Zeebregts
authors.affiliation: Departments of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, PB 30.001, 9700 RB, Groningen, The Netherlands.
authors.forename: Johanna
authors.initials: J
authors.lastname: Westra
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016893:Carotid Stenosis / Q000201:enzymology* / Q000473:pathology; D003710:Demography; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005453:Fluorescence; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008264:Macrophages / Q000201:enzymology* / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000201:enzymology* / Q000473:pathology; D058226:Plaque, Atherosclerotic / Q000201:enzymology* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors
chemical_list: D012333:RNA, Messenger; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: Atherosclerotic plaque; MMPSense; Macrophage; Matrix metalloproteinase; Smooth muscle cell