title: The effects of pharmacologic plasminogen activator inhibitor-1 inhibition in acute and chronic rejection in murine cardiac allografts.
abstract: BACKGROUND
  Acute rejection and graft arterial disease (GAD) in cardiac transplantation limit the long-term survival of recipients; these processes are enhanced by inflammation and thrombus formation. Plasminogen activator inhibitor (PAI)-1 is critical in the inflammation and thrombus formation. However, little is known about the effect of PAI-1 in heart transplantation. Thus, the objective was to clarify the role of PAI-1 in the progression of cardiac rejection.
  
  
  METHODS
  Murine hearts were heterotopically transplanted using major mismatch combinations for evaluation of acute rejection and class II mismatch combinations for the GAD. We administered the specific PAI-1 inhibitor (IMD-1622) into murine recipients after cardiac allografts.
  
  
  RESULTS
  Nontreated allografts of the major mismatch group were acutely rejected, whereas the PAI-1 inhibitor prolonged their survival. Although severe cell infiltration and intimal thickening with enhancement of inflammatory factors were observed in untreated allografts of class II mismatch group on day 60, the PAI-1 inhibitor attenuated these changes.
  
  
  CONCLUSIONS
  The PAI-1 inhibitor is potent for the suppression of both acute rejection and GAD.
authors: Department of Advanced Clinical Science and Therapeutics, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors: Masahito
authors: M
authors: Ogawa
authors: Jun-ichi
authors: J
authors: Suzuki
authors: Yoichi
authors: Y
authors: Yamaguchi
authors: Susumu
authors: S
authors: Muto
authors: Akiko
authors: A
authors: Itai
authors: Yasunobu
authors: Y
authors: Hirata
authors: Mitsuaki
authors: M
authors: Isobe
authors: Ryozo
authors: R
authors: Nagai
mesh_terms: D000208:Acute Disease; D000818:Animals; D002318:Cardiovascular Diseases / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D006084:Graft Rejection / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D016027:Heart Transplantation / Q000276:immunology*; D051379:Mice; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: C530962:3-(3,4-dichlorobenzyl)-5-(3,4,5-trihydroxybenzylidene)thiazolidine-2,4-dione; D017395:Plasminogen Activator Inhibitor 1; D045162:Thiazolidinediones