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Soluble CD40 levels in plasma are associated with cardiovascular disease and in carotid plaques with a vulnerable phenotype

Shami, Annelie LU orcid ; Edsfeldt, Andreas LU ; Bengtsson, Eva LU orcid ; Nilsson, Jan LU ; Shore, Angela C. ; Natali, Andrea ; Khan, Faisel ; Lutgens, Esther and Gonçalves, Isabel LU orcid (2021) In Journal of Stroke 23(3). p.367-376
Abstract

Background and Purpose CD40 and CD40 ligand (CD40L) are costimulatory molecules of the tumor necrosis factor receptor superfamily and well known for their involvement in inflammatory diseases: atherosclerotic mouse models with disrupted CD40 signalling develop lesions of reduced size with a more stable plaque profile. This study investigated the potential of plasma and intraplaque levels of CD40 and CD40L as markers for cardiovascular disease (CVD) in humans and their association with plaque stability. Methods Soluble CD40 and CD40L (sCD40L) were measured in plasma in 1,437 subjects from The SUrrogate markers for Micro-and Macro-vascular hard endpoints for Innovative diabetes Tools (SUMMIT) cohort. Intra-plaque levels of sCD40 and... (More)

Background and Purpose CD40 and CD40 ligand (CD40L) are costimulatory molecules of the tumor necrosis factor receptor superfamily and well known for their involvement in inflammatory diseases: atherosclerotic mouse models with disrupted CD40 signalling develop lesions of reduced size with a more stable plaque profile. This study investigated the potential of plasma and intraplaque levels of CD40 and CD40L as markers for cardiovascular disease (CVD) in humans and their association with plaque stability. Methods Soluble CD40 and CD40L (sCD40L) were measured in plasma in 1,437 subjects from The SUrrogate markers for Micro-and Macro-vascular hard endpoints for Innovative diabetes Tools (SUMMIT) cohort. Intra-plaque levels of sCD40 and sCD40L were measured in atherosclerotic plaque homogenates from 199 subjects of the Carotid Plaque Imaging Project (CPIP) cohort. Results Both plasma sCD40 and sCD40L levels were elevated in individuals with prevalent stroke, while sCD40 levels also were higher in individuals with a prior acute myocardial infarction. Plasma levels of sCD40 correlated with carotid intima-media thickness and total carotid plaque area and were associated with risk of cardiovascular events over a 3-year follow-up period. Intra-plaque levels of sCD40 and sCD40L were associated with plaque components characteristic for plaque vulnerability and extracellular matrix remodelling. Conclusions Higher plasma sCD40 and sCD40L levels are associated with prevalent CVD. Plasma sCD40 levels also correlate with the severity of carotid atherosclerosis and predict future cardiovascular events, while intra-plaque levels correlate with a vulnerable plaque phenotype. Our findings thus demonstrate that elevated levels of sCD40 and sCD40L are markers of CVD.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Atherosclerosis, Carotid arteries, CD40, CD40 ligand, Inflammation
in
Journal of Stroke
volume
23
issue
3
pages
10 pages
publisher
KOREAN STROKE SOC
external identifiers
  • scopus:85120781609
  • pmid:34649381
ISSN
2287-6391
DOI
10.5853/jos.2021.00178
language
English
LU publication?
yes
id
4b93999e-1e63-4857-bbae-fddd5897ead1
date added to LUP
2022-02-03 12:44:30
date last changed
2024-06-18 06:30:39
@article{4b93999e-1e63-4857-bbae-fddd5897ead1,
  abstract     = {{<p>Background and Purpose CD40 and CD40 ligand (CD40L) are costimulatory molecules of the tumor necrosis factor receptor superfamily and well known for their involvement in inflammatory diseases: atherosclerotic mouse models with disrupted CD40 signalling develop lesions of reduced size with a more stable plaque profile. This study investigated the potential of plasma and intraplaque levels of CD40 and CD40L as markers for cardiovascular disease (CVD) in humans and their association with plaque stability. Methods Soluble CD40 and CD40L (sCD40L) were measured in plasma in 1,437 subjects from The SUrrogate markers for Micro-and Macro-vascular hard endpoints for Innovative diabetes Tools (SUMMIT) cohort. Intra-plaque levels of sCD40 and sCD40L were measured in atherosclerotic plaque homogenates from 199 subjects of the Carotid Plaque Imaging Project (CPIP) cohort. Results Both plasma sCD40 and sCD40L levels were elevated in individuals with prevalent stroke, while sCD40 levels also were higher in individuals with a prior acute myocardial infarction. Plasma levels of sCD40 correlated with carotid intima-media thickness and total carotid plaque area and were associated with risk of cardiovascular events over a 3-year follow-up period. Intra-plaque levels of sCD40 and sCD40L were associated with plaque components characteristic for plaque vulnerability and extracellular matrix remodelling. Conclusions Higher plasma sCD40 and sCD40L levels are associated with prevalent CVD. Plasma sCD40 levels also correlate with the severity of carotid atherosclerosis and predict future cardiovascular events, while intra-plaque levels correlate with a vulnerable plaque phenotype. Our findings thus demonstrate that elevated levels of sCD40 and sCD40L are markers of CVD.</p>}},
  author       = {{Shami, Annelie and Edsfeldt, Andreas and Bengtsson, Eva and Nilsson, Jan and Shore, Angela C. and Natali, Andrea and Khan, Faisel and Lutgens, Esther and Gonçalves, Isabel}},
  issn         = {{2287-6391}},
  keywords     = {{Atherosclerosis; Carotid arteries; CD40; CD40 ligand; Inflammation}},
  language     = {{eng}},
  month        = {{09}},
  number       = {{3}},
  pages        = {{367--376}},
  publisher    = {{KOREAN STROKE SOC}},
  series       = {{Journal of Stroke}},
  title        = {{Soluble CD40 levels in plasma are associated with cardiovascular disease and in carotid plaques with a vulnerable phenotype}},
  url          = {{http://dx.doi.org/10.5853/jos.2021.00178}},
  doi          = {{10.5853/jos.2021.00178}},
  volume       = {{23}},
  year         = {{2021}},
}