title: Identification of a potential cardiac antifibrotic mechanism of torasemide in patients with chronic heart failure.
abstract: OBJECTIVE
  This study sought to investigate whether torasemide inhibits the enzyme involved in the myocardial extracellular generation of collagen type I molecules (i.e., procollagen type I carboxy-terminal proteinase [PCP]).
  
  
  BACKGROUND
  Torasemide has been reported to reduce myocardial fibrosis in patients with chronic heart failure (HF).
  
  
  METHODS
  Chronic HF patients received either 10 to 20 mg/day oral torasemide (n = 11) or 20 to 40 mg/day oral furosemide (n = 11) in addition to their standard HF therapy. At baseline and after 8 months from randomization, right septal endomyocardial biopsies were obtained to analyze the expression of PCP by Western blot and the deposition of collagen fibers (collagen volume fraction [CVF]) with an automated image analysis system. The carboxy-terminal propeptide of procollagen type I (PICP) released as a result of the action of PCP on procollagen type I was measured in serum by radioimmunoassay.
  
  
  RESULTS
  The ratio of PCP active form to PCP zymogen, an index of PCP activation, decreased (p < 0.05) in torasemide-treated patients and remained unchanged in furosemide-treated patients. A reduction (p < 0.01) in both CVF and PICP was observed in torasemide-treated but not in furosemide-treated patients. Changes in PCP activation were positively correlated (p < 0.001) with changes in CVF and changes in PICP in patients receiving torasemide.
  
  
  CONCLUSIONS
  These findings suggest the hypothesis that the ability of torasemide to reduce myocardial fibrosis in chronic HF patients is related to a decreased PCP activation. Further studies are required to ascertain whether PCP may represent a new target for antifibrotic strategies in chronic HF.
authors: Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain.
authors: Begoña
authors: B
authors: López
authors: Arantxa
authors: A
authors: González
authors: Javier
authors: J
authors: Beaumont
authors: Ramón
authors: R
authors: Querejeta
authors: Mariano
authors: M
authors: Larman
authors: Javier
authors: J
authors: Díez
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D015153:Blotting, Western; D004699:Endocardium / Q000473:pathology; D005109:Extracellular Matrix; D005260:Female; D005355:Fibrosis / Q000188:drug therapy; D005665:Furosemide / Q000494:pharmacology / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D010446:Peptide Fragments / Q000097:blood / Q000378:metabolism; D010865:Pilot Projects; D011347:Procollagen / Q000097:blood / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000077786:Torsemide
chemical_list: D000959:Antihypertensive Agents; D010446:Peptide Fragments; D011347:Procollagen; D013449:Sulfonamides; C042813:procollagen type I carboxy terminal peptide; D005665:Furosemide; D000077786:Torsemide