title: Altered expression of ADAMs (A Disintegrin And Metalloproteinase) in fibrillating human atria.
abstract: BACKGROUND
  ADAMs (A Disintegrin And Metalloproteinase) are ectoproteases that have recently been reported to be expressed in cardiac tissue. Although they are known to regulate cell-cell and cell-matrix interactions, their pathophysiological role in various cardiac diseases is unclear. The purpose of the present study was to determine whether structural remodeling of the atria during atrial fibrillation (AF) is associated with altered ADAM expression.
  
  
  RESULTS
  Atrial tissue samples of 30 patients undergoing open-heart surgery were examined. Fifteen patients had persistent AF (> or =6 months), and the remaining 15 patients had no history of AF. ADAM9, ADAM10, and ADAM15 expression was analyzed quantitatively at the mRNA and protein levels. ADAM expression was localized by immunohistochemistry. ADAM expression was correlated with amounts of integrins beta1 and beta3. The amount of ADAM10 protein more than doubled during AF (82+/-15 versus 36+/-8 U; P<0.01). Amounts of ADAM15 protein (102+/-12 versus 40+/-6 U; P<0.01) and mRNA (24.0+/-5.6 versus 10.5+/-2.5 U; P<0.05) increased significantly during AF compared with sinus rhythm. ADAM9 protein was not detected in any sample. ADAM/integrin ratios showed an increase of 4- to 6-fold (P<0.05) in patients with AF who had significantly dilated atria (4.94+/-0.6 versus 4.3+/-0.7 cm; P<0.05). ADAM/integrin ratios correlated with atrial diameter.
  
  
  CONCLUSIONS
  AF is associated with an increase in the expression of ADAM10 and ADAM15. Enhanced ADAM-dependent disintegrin and metalloproteinase activity may be a molecular mechanism that contributes to the dilation of fibrillating human atria.
authors.affiliation: Institute of Experimental Internal Medicine, University Hospital Magdeburg, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Arndt
authors.forename: Uwe
authors.initials: U
authors.lastname: Lendeckel
authors.forename: Christoph
authors.initials: C
authors.lastname: Röcken
authors.forename: Karen
authors.initials: K
authors.lastname: Nepple
authors.forename: Carmen
authors.initials: C
authors.lastname: Wolke
authors.forename: Antje
authors.initials: A
authors.lastname: Spiess
authors.forename: Christof
authors.initials: C
authors.lastname: Huth
authors.forename: Siegfried
authors.initials: S
authors.lastname: Ansorge
authors.forename: Helmut U
authors.initials: HU
authors.lastname: Klein
authors.forename: Andreas
authors.initials: A
authors.lastname: Goette
mesh_terms: D051722:ADAM Proteins; D000072197:ADAM10 Protein; D000328:Adult; D000368:Aged; D053829:Amyloid Precursor Protein Secretases; D015703:Antigens, CD / Q000378:metabolism; D020517:Atrial Appendage / Q000737:chemistry / Q000503:physiopathology / Q000601:surgery; D001281:Atrial Fibrillation / Q000150:complications / Q000503:physiopathology* / Q000601:surgery; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism; D019483:Disintegrins / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006325:Heart Atria / Q000737:chemistry / Q000503:physiopathology* / Q000601:surgery; D006331:Heart Diseases / Q000150:complications / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D019012:Integrin beta1 / Q000378:metabolism; D039661:Integrin beta3; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D019483:Disintegrins; D019012:Integrin beta1; D039661:Integrin beta3; D008565:Membrane Proteins; D009124:Muscle Proteins; D010980:Platelet Membrane Glycoproteins; D012333:RNA, Messenger; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; C098660:ADAM15 protein, human; C098339:ADAM9 protein, human; D008666:Metalloendopeptidases; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human