title: Nitric oxide promotes in vitro interstitial cell heart valve repair.
abstract: BACKGROUND
  The cell and molecular biology of heart valve wound repair is not well understood. Valve interstitial cells (IC) are thought to play an important role in valvular wound repair. Because nitric oxide (NO) has been implicated in wound repair, we tested the hypothesis that NO promotes valvular wound repair by examining the presence of the inducible form of nitric oxide synthase (iNOS) in wounded IC monolayers, in vitro.
  
  
  METHODS
  Linear denuding wounds were made in confluent monolayers of porcine mitral valve IC plated on glass coverslips. Cultures were fixed at various times (0 to 48 h postwounding), and iNOS was localized in the cells by immunofluorescence microscopy. Cultures were also incubated with iNOS inhibitors L-N(G)-nitroarginine methyl ester (L-NAME) and N-(3-(Aminomethyl)benzyl)acetamidine (1400W), and the extent of wound closure with and without inhibitor was measured at 24, 48 and 72 h postwounding.
  
  
  RESULTS
  From 6 to 24 h postwounding, iNOS localization was increased at the wound edge. At 48 h, iNOS was localized beyond the wound edge, into the monolayer, where the intensity of the signal gradually diminished until it was virtually imperceptible. At 24 and 48 h, the inhibition of iNOS with both L-NAME and 1400W resulted in a significant delay in wound closure.
  
  
  CONCLUSIONS
  NO promotes valve wound repair through an effect on IC migration.
authors.affiliation: Toronto General Research Institute, Toronto, ON, Canada.
authors.forename: Adam
authors.initials: A
authors.lastname: Durbin
authors.forename: Nur-Ain
authors.initials: NA
authors.lastname: Nadir
authors.forename: Alan
authors.initials: A
authors.lastname: Rosenthal
authors.forename: Avrum I
authors.initials: AI
authors.lastname: Gotlieb
mesh_terms: D000578:Amidines / Q000494:pharmacology; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019084:Fluorescent Antibody Technique, Indirect; D008943:Mitral Valve / Q000166:cytology* / Q000201:enzymology / Q000293:injuries; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D013552:Swine; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
chemical_list: D000578:Amidines; D001596:Benzylamines; D004791:Enzyme Inhibitors; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D019331:NG-Nitroarginine Methyl Ester