title: Regulation of cardiomyocyte full-length tissue factor expression and microparticle release under inflammatory conditions in vitro.
abstract: BACKGROUND
  Myocardial inflammation is associated with an increase in circulating microparticles (MPs) and procoagulability.
  
  
  OBJECTIVE
  We determined whether acute inflammation was associated with altered full-length tissue factor (flTF) expression and increased procoagulability in cardiomyocytic cells.
  
  
  METHODS
  This study examined the transcriptional regulation of flTF expression in murine cardiomyocytic (HL-1) cells. Also, the generation of MPs by HL-1 cells and their ability to diffuse through an artificial endothelium was evaluated.
  
  
  RESULTS
  Constitutive and tumor necrosis factor-alpha (TNF-alpha)-induced flTF expression of HL-1 was reduced when c-Jun N-terminal kinase (JNK) was inhibited. Tissue factor (TF)-positive procoagulant MPs were released from HL-1 cells in response to TNF-alpha. JNK inhibition potentiated the release of MPs from HL-1 cells without affecting MP-associated TF activity. MP generation was dependent on RhoA activation and associated with a reorganization of the actin cytoskeleton. Increased diffusion of HL-1-derived MPs through an endothelial monolayer was found after TNF-alpha treatment. The increased diffusion was dependent not only on TNF-alpha but also on HL-1-released mediators.
  
  
  CONCLUSIONS
  Full-length TF expression in HL-1 cells was regulated through JNK. The TNF-alpha-induced increase in procoagulability was mediated through RhoA-dependent release of flTF-bearing MPs. These MPs were able to diffuse through an endothelial barrier adjacent to HL-1 cells and increased the procoagulability of the extracellular endothelial space. Cardiomyocytes seem to be a likely source of flTF-bearing procoagulant MPs.
authors.affiliation: Department of Cardiology and Pneumology, CharitéCentrum 11 - Herz-, Kreislauf- und Gefässmedizin, Charité- Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Antoniak
authors.forename: U
authors.initials: U
authors.lastname: Boltzen
authors.forename: A
authors.initials: A
authors.lastname: Eisenreich
authors.forename: C
authors.initials: C
authors.lastname: Stellbaum
authors.forename: W
authors.initials: W
authors.lastname: Poller
authors.forename: H P
authors.initials: HP
authors.lastname: Schultheiss
authors.forename: U
authors.initials: U
authors.lastname: Rauch
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D018920:Coculture Techniques; D007249:Inflammation / Q000378:metabolism*; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000199:Actins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013925:Thromboplastin