title: Pericardial fluid from patients with unstable angina induces vascular endothelial cell apoptosis.
abstract: OBJECTIVE
  The purpose of this study was to investigate whether pericardial fluid from patients with unstable angina (UA) would modulate vascular endothelial cell survival.
  
  
  BACKGROUND
  Apoptosis of vascular endothelial cells promotes the coagulation process, playing an important role in the formation of coronary arterial thrombi. However, little is known about the mechanisms of vascular endothelial cell death in acute coronary syndrome. We hypothesized that factors inducing apoptosis are produced by the ischemic heart and accumulated in high concentrations in pericardial fluid.
  
  
  METHODS
  Pericardial fluid was obtained during coronary artery bypass surgery from patients with UA (group A, n = 8) and those with stable angina (group B, n = 23). A survival assay of F2 cells from a mouse vascular endothelial cell line was performed in the presence of 10% pericardial fluid from each patient.
  
  
  RESULTS
  Pericardial fluid levels of vascular endothelial growth factor were significantly higher in group A than in group B, indicating that group A had more ischemic insults than group B. Pericardial fluid from group A, but not from group B, markedly induced F2 cell death (cell survival relative to fetal bovine serum; group A: 33 +/- 26% vs. group B: 91 +/- 22%, p < 0.01). Cell death was associated with internucleosomal DNA fragmentation, a hallmark of apoptosis. Fractionation of pericardial fluid using a Centricon C-100 demonstrated that apoptosis-inducible activities exist in the Centricon C-100 retentates but not in the filtrates.
  
  
  CONCLUSIONS
  Factors that induce vascular endothelial cell apoptosis are secreted into the pericardial space from the hearts of patients with UA. These factors are large complexes or unknown new proteins larger than 100 kDa.
authors.affiliation: Department of Cardiovascular Surgery, Kyoto University, Graduate School of Medicine, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Iwakura
authors.forename: M
authors.initials: M
authors.lastname: Fujita
authors.forename: K
authors.initials: K
authors.lastname: Hasegawa
authors.forename: T
authors.initials: T
authors.lastname: Sawamura
authors.forename: R
authors.initials: R
authors.lastname: Nohara
authors.forename: S
authors.initials: S
authors.lastname: Sasayama
authors.forename: M
authors.initials: M
authors.lastname: Komeda
mesh_terms: D000368:Aged; D000789:Angina, Unstable / Q000473:pathology*; D017209:Apoptosis; D001826:Body Fluids / Q000737:chemistry / Q000502:physiology*; D002470:Cell Survival; D016228:Endothelial Growth Factors / Q000032:analysis; D004730:Endothelium, Vascular / Q000473:pathology*; D005260:Female; D006801:Humans; D008222:Lymphokines / Q000032:analysis; D008297:Male; D010496:Pericardium; D020033:Protein Isoforms / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D008222:Lymphokines; D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors