title: Alterations in myocardial tissue factor expression and cellular localization in dilated cardiomyopathy.
abstract: OBJECTIVE
  We investigated the myocardial localization and expression of tissue factor (TF) and alternatively spliced human tissue factor (asHTF) in patients with dilated cardiomyopathy (DCM).
  
  
  BACKGROUND
  Tissue factor is expressed in cardiac muscle and may play a role in maintaining myocardial structure.
  
  
  METHODS
  Myocardial biopsies were obtained from patients with a normal or mildly impaired ejection fraction (EF) (> or =50%) and moderate to severely reduced EF (<50%). Explanted DCM hearts were also examined. Myocardial TF expression level was assessed by real-time polymerase chain reaction, TF protein by enzyme-linked immunosorbent assay, and localization by immunohistochemistry.
  
  
  RESULTS
  We report the identification of asHTF in the human myocardium: it was located in cardiomyocytes and endothelial cells. Quantification of myocardial TF messenger ribonucleic acid in DCM revealed a decrease in the TF/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) ratio (1.76 x 10(-1) +/- 6.08 x 10(-2) for EF > or =50% [n = 19] vs. 1.06 x 10(-1) +/- 5.26 x 10(-2) for EF <50% [n = 27]; p < 0.001) and asHTF/GAPDH ratio (13.91 x 10(-5) +/- 11.20 x 10(-5) for EF > or =50% vs. 7.17 x 10(-5) +/- 3.82 x 10(-5) for EF <50%; p = 0.014). Tissue factor isoform expression level was also decreased in explanted DCM hearts (p < 0.01; n = 12). Total TF protein was reduced by 26% in DCM (p < 0.05). The TF/GAPDH ratio correlated positively with the EF (r = 0.504, p < 0.0001). Immunohistochemistry showed TF localized to the sarcolemma and Z-bands of the cardiomyocytes in patients with normal EF, whereas TF was found in the cardiomyocytic cytosol around the nucleus in DCM.
  
  
  CONCLUSIONS
  Tissue factor was down-regulated in the myocardium of DCM patients. The reduction in TF expression and change in localization may influence cell-to-cell contact stability and contractility, thereby contributing to cardiac dysfunction in DCM.
authors.affiliation: Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Szotowski
authors.forename: Petra
authors.initials: P
authors.lastname: Goldin-Lang
authors.forename: Silvio
authors.initials: S
authors.lastname: Antoniak
authors.forename: Vladimir Y
authors.initials: VY
authors.lastname: Bogdanov
authors.forename: Delano
authors.initials: D
authors.lastname: Pathirana
authors.forename: Matthias
authors.initials: M
authors.lastname: Pauschinger
authors.forename: Andrea
authors.initials: A
authors.lastname: Dörner
authors.forename: Uwe
authors.initials: U
authors.lastname: Kuehl
authors.forename: Sarah
authors.initials: S
authors.lastname: Coupland
authors.forename: Yale
authors.initials: Y
authors.lastname: Nemerson
authors.forename: Michael
authors.initials: M
authors.lastname: Hummel
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Poller
authors.forename: Roland
authors.initials: R
authors.lastname: Hetzer
authors.forename: Heinz-Peter
authors.initials: HP
authors.lastname: Schultheiss
authors.forename: Ursula
authors.initials: U
authors.lastname: Rauch
mesh_terms: D015153:Blotting, Western; D002311:Cardiomyopathy, Dilated / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D017931:DNA Primers; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D013925:Thromboplastin