title: The involvement of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in atherosclerosis.
abstract: OBJECTIVE
  Herein, we determined the significance of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in atherosclerotic vascular disease.
  
  
  BACKGROUND
  Inflammation is associated with the pathogenesis of atherosclerosis. The TNF-related apoptosis-inducing ligand/APO-2L, a member of the TNF superfamily, has a role in apoptosis induction and is recognized for its immunomodulatory properties.
  
  
  METHODS
  Stable and vulnerable atherosclerotic human plaques and aortas from atherosclerotic mice were assayed for the presence of TRAIL, and its inducibility was assayed by immunoblot and real-time polymerase chain reaction on peripheral mononuclear cells incubated with oxidized low-density lipoprotein (oxLDL). Enzyme-linked immunosorbent assay was used for the determination of soluble TRAIL levels in atherosclerotic patients.
  
  
  RESULTS
  Tumor necrosis factor-related apoptosis-inducing ligand is present in stable atherosclerotic lesions, is increased in vulnerable plaques, and is found to colocalize with CD3 cells and oxLDL. The TNF-related apoptosis-inducing ligand messenger ribonucleic acid (mRNA) and protein expression was up-regulated in peripheral blood mononuclear cells after incubation with oxLDL. Serum levels of soluble TRAIL but not TNF-alpha or Fas-ligand were reduced significantly in patients with unstable angina as compared with patients with stable atherosclerotic disease and healthy subjects. A negative correlation was demonstrated between soluble TRAIL and C-reactive protein levels but not with levels of mRNA of TRAIL in peripheral blood mononuclear cells.
  
  
  CONCLUSIONS
  Tumor necrosis factor-related apoptosis-inducing ligand is expressed in plaque-infiltrating CD3 cells and induced by oxLDL, whereas levels of soluble TRAIL are reduced in patients with acute coronary syndromes and negatively correlate with C-reactive protein levels. These results support a possible role for TRAIL in atherosclerosis.
authors.affiliation: Department of Cardiology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Michowitz
authors.forename: Emil
authors.initials: E
authors.lastname: Goldstein
authors.forename: Arie
authors.initials: A
authors.lastname: Roth
authors.forename: Arnon
authors.initials: A
authors.lastname: Afek
authors.forename: Anastasia
authors.initials: A
authors.lastname: Abashidze
authors.forename: Yanai
authors.initials: Y
authors.lastname: Ben Gal
authors.forename: Gad
authors.initials: G
authors.lastname: Keren
authors.forename: Jacob
authors.initials: J
authors.lastname: George
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000097:blood*; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D019014:fas Receptor
chemical_list: D051017:Apoptosis Regulatory Proteins; D017931:DNA Primers; D008024:Ligands; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor