title: Extracellular matrix metalloproteinase inducer regulates matrix metalloproteinase activity in cardiovascular cells: implications in acute myocardial infarction.
abstract: BACKGROUND
  Matrix metalloproteinases (MMPs) are thought to promote progression of atherosclerosis and cardiovascular complications such as plaque rupture. It has been suggested that, on tumor cells, the extracellular MMP inducer (EMMPRIN) is involved in MMP synthesis by as yet unknown mechanisms. On cardiovascular cells, regulation of EMMPRIN in vivo or any functional relevance for MMP induction in vitro has not yet been studied. Thus, we studied EMMPRIN expression on monocytes in acute myocardial infarction (MI) and its potential relevance for MMP activation.
  
  
  RESULTS
  In 20 patients with acute MI, surface expression of EMMPRIN was significantly enhanced on monocytes compared with in 20 patients with chronic stable angina. EMMPRIN upregulation was associated with increased expression of the membrane type 1 MMP (MT1-MMP) on monocytes (flow cytometry) as well as MMP-9 activity (gelatin zymography) in the plasma. At 6 months after successful revascularization, EMMPRIN, MT1-MMP, and MMP-9 had normalized. The secretion of MMP-9 by monocytes was induced by monocyte adhesion to immobilized recombinant EMMPRIN or to EMMPRIN-transfected Chinese hamster ovary cells. Moreover, adherent EMMPRIN-transfected monocytic cells stimulated MMP-2 activity of human vascular smooth muscle cells. Gene silencing of EMMPRIN by small-interfering RNA hindered lipopolysaccharide-induced monocyte secretion of MMP-9, indicating a predominant role of EMMPRIN in MMP-9 induction.
  
  
  CONCLUSIONS
  EMMPRIN and MT1-MMP are upregulated on monocytes in acute MI. During cellular interactions, EMMPRIN stimulates MMP-9 in monocytes and MMP-2 in smooth muscle cells, indicating that EMMPRIN may display a key regulatory role for MMP activity in cardiovascular pathologies.
authors.affiliation: Deutsches Herzzentrum und Medizinische Klinik I, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Schmidt
authors.forename: Andreas
authors.initials: A
authors.lastname: Bültmann
authors.forename: Martin
authors.initials: M
authors.lastname: Ungerer
authors.forename: Nader
authors.initials: N
authors.lastname: Joghetaei
authors.forename: Ozgür
authors.initials: O
authors.lastname: Bülbül
authors.forename: Sven
authors.initials: S
authors.lastname: Thieme
authors.forename: Triantafyllos
authors.initials: T
authors.lastname: Chavakis
authors.forename: Bryan P
authors.initials: BP
authors.lastname: Toole
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz
authors.forename: Albert
authors.initials: A
authors.lastname: Schömig
authors.forename: Andreas E
authors.initials: AE
authors.lastname: May
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis; D051926:Basigin / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D002448:Cell Adhesion; D004789:Enzyme Activation; D016326:Extracellular Matrix Proteins; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D009203:Myocardial Infarction / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D015854:Up-Regulation
chemical_list: C497886:BSG protein, human; D016326:Extracellular Matrix Proteins; D051926:Basigin; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D020780:Matrix Metalloproteinase 9