TY - JOUR
T1 - The involvement of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in atherosclerosis
AU - Michowitz, Yoav
AU - Goldstein, Emil
AU - Roth, Arie
AU - Afek, Arnon
AU - Abashidze, Anastasia
AU - Ben Gal, Yanai
AU - Keren, Gad
AU - George, Jacob
PY - 2005/4/1
Y1 - 2005/4/1
N2 - OBJECTIVES: 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.
AB - OBJECTIVES: 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.
UR - http://www.scopus.com/inward/record.url?scp=15944425098&partnerID=8YFLogxK
U2 - 10.1016/j.jacc.2004.12.065
DO - 10.1016/j.jacc.2004.12.065
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AN - SCOPUS:15944425098
VL - 45
SP - 1018
EP - 1024
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
SN - 0735-1097
IS - 7
ER -
