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LIGHT/TNFSF14 Levels in Carotid Plaques Are Associated With Symptomatic Cerebrovascular Disease

Gonçalves, Isabel LU orcid ; Sun, Jiangming LU orcid ; Singh, Pratibha LU ; Pan, Mengyu LU orcid ; Gialeli, Chrysostomi LU ; Bengtsson, Eva LU orcid ; Nilsson, Jan LU ; Lutgens, Esther ; Edsfeldt, Andreas LU orcid and Shami, Annelie LU orcid (2025) In Journal of Stroke 27(3). p.381-389
Abstract

Background and Purpose Plaque rupture is the underlying cause of most cardiovascular events, such as stroke and myocardial infarction. The co-stimulatory molecule LIGHT (tumor necrosis factor superfamily member 14, TNFSF14) has been detected in foam cell-rich regions of atherosclerotic plaques, but whether it has a role in plaque stability is not known. This study investigates the association between intraplaque LIGHT levels and plaque vulnerability. Methods LIGHT levels were measured in homogenates of carotid endarterectomy samples by proximity extension assay (n=202) and through bulk RNA sequencing and spatial transcriptomics (Visium) of plaques from patients included in the Carotid Plaque Imaging Project. Homogenates were further... (More)

Background and Purpose Plaque rupture is the underlying cause of most cardiovascular events, such as stroke and myocardial infarction. The co-stimulatory molecule LIGHT (tumor necrosis factor superfamily member 14, TNFSF14) has been detected in foam cell-rich regions of atherosclerotic plaques, but whether it has a role in plaque stability is not known. This study investigates the association between intraplaque LIGHT levels and plaque vulnerability. Methods LIGHT levels were measured in homogenates of carotid endarterectomy samples by proximity extension assay (n=202) and through bulk RNA sequencing and spatial transcriptomics (Visium) of plaques from patients included in the Carotid Plaque Imaging Project. Homogenates were further examined by multiplex analyses and enzyme-linked immunosorbent assay, and plaque sections by immunohistochemistry. Results Plaque levels of LIGHT were associated with occurrence of preoperative cerebrovascular symptoms, including stroke. LIGHT levels correlated with a histological plaque vulnerability index, necrotic core size, and inflammatory cytokine levels. Additionally, expression of extracellular matrix turnover machinery components, including the collagen cross-linking proteoglycan fibromodulin and matrix metalloproteinases 1, 2, 9, and 10, was associated with plaque LIGHT levels. Conclusion Expression of LIGHT in atherosclerotic plaques not only correlates with markers of plaque destabilization, but is also significantly elevated in plaques from symptomatic compared to those from asymptomatic patients. These results associate LIGHT content with a rupture-prone plaque phenotype, potentially upregulated as part of a reparative response, warranting further studies.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Atherosclerosis, Carotid arteries, Plaque, TNFSF14
in
Journal of Stroke
volume
27
issue
3
pages
9 pages
publisher
Korean Stroke Society
external identifiers
  • pmid:41084292
  • scopus:105018749449
ISSN
2287-6391
DOI
10.5853/jos.2025.00703
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2025 Korean Stroke Society.
id
2103a87c-d9a5-401a-a7a1-678b0993a670
date added to LUP
2025-12-18 12:51:14
date last changed
2025-12-19 03:17:09
@article{2103a87c-d9a5-401a-a7a1-678b0993a670,
  abstract     = {{<p>Background and Purpose Plaque rupture is the underlying cause of most cardiovascular events, such as stroke and myocardial infarction. The co-stimulatory molecule LIGHT (tumor necrosis factor superfamily member 14, TNFSF14) has been detected in foam cell-rich regions of atherosclerotic plaques, but whether it has a role in plaque stability is not known. This study investigates the association between intraplaque LIGHT levels and plaque vulnerability. Methods LIGHT levels were measured in homogenates of carotid endarterectomy samples by proximity extension assay (n=202) and through bulk RNA sequencing and spatial transcriptomics (Visium) of plaques from patients included in the Carotid Plaque Imaging Project. Homogenates were further examined by multiplex analyses and enzyme-linked immunosorbent assay, and plaque sections by immunohistochemistry. Results Plaque levels of LIGHT were associated with occurrence of preoperative cerebrovascular symptoms, including stroke. LIGHT levels correlated with a histological plaque vulnerability index, necrotic core size, and inflammatory cytokine levels. Additionally, expression of extracellular matrix turnover machinery components, including the collagen cross-linking proteoglycan fibromodulin and matrix metalloproteinases 1, 2, 9, and 10, was associated with plaque LIGHT levels. Conclusion Expression of LIGHT in atherosclerotic plaques not only correlates with markers of plaque destabilization, but is also significantly elevated in plaques from symptomatic compared to those from asymptomatic patients. These results associate LIGHT content with a rupture-prone plaque phenotype, potentially upregulated as part of a reparative response, warranting further studies.</p>}},
  author       = {{Gonçalves, Isabel and Sun, Jiangming and Singh, Pratibha and Pan, Mengyu and Gialeli, Chrysostomi and Bengtsson, Eva and Nilsson, Jan and Lutgens, Esther and Edsfeldt, Andreas and Shami, Annelie}},
  issn         = {{2287-6391}},
  keywords     = {{Atherosclerosis; Carotid arteries; Plaque; TNFSF14}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{381--389}},
  publisher    = {{Korean Stroke Society}},
  series       = {{Journal of Stroke}},
  title        = {{LIGHT/TNFSF14 Levels in Carotid Plaques Are Associated With Symptomatic Cerebrovascular Disease}},
  url          = {{http://dx.doi.org/10.5853/jos.2025.00703}},
  doi          = {{10.5853/jos.2025.00703}},
  volume       = {{27}},
  year         = {{2025}},
}