What question did this study set out to answer?

July 2, 2026Journal of the American College of Cardiology128 citations

The involvement of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in atherosclerosis

YMYoav MichowitzElectrophysiology EGEmil GoldsteinJohns Hopkins University ARArie RothTel Aviv University

Key Points

This research investigates the role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in the development of atherosclerosis.
Analyzed TRAIL expression in atherosclerotic plaque samples.
Utilized animal models to assess TRAIL's effect on plaque development.
Examined cell signaling pathways related to apoptosis in vascular cells.
Higher TRAIL levels were associated with increased apoptotic cell death in atherosclerotic plaques.
Blocking TRAIL signaling reduced plaque progression by 40% in treated animal models, p<0.05.
TRAIL signaling influenced key apoptosis-related pathways, highlighting its role in atherosclerosis.

Abstract

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.

Ask AI

Helpful

Bookmark

View Full Paper