4.6 Article

Soluble CD40 Levels in Plasma Are Associated with Cardiovascular Disease and in Carotid Plaques with a Vulnerable Phenotype

Journal

JOURNAL OF STROKE
Volume 23, Issue 3, Pages 367-+

Publisher

KOREAN STROKE SOC
DOI: 10.5853/jos.2021.00178

Keywords

CD40; CD40 ligand; Atherosclerosis; Carotid arteries; Inflammation

Funding

  1. Swedish Foundation for Strategic Research [Dnr IRC15-0067] Funding Source: Medline
  2. Swedish Heart and Lung Foundation Funding Source: Medline
  3. Swedish Research Council Funding Source: Medline
  4. The Swedish Heart and Lung Association Funding Source: Medline
  5. UK National Institute of Health Research Funding Source: Medline
  6. Stroke Foundation Funding Source: Medline
  7. Swedish Society for Medical Research Funding Source: Medline
  8. Diabetes foundation Funding Source: Medline
  9. Albert Påhlsson's foundation Funding Source: Medline
  10. SUS foundations and funds Funding Source: Medline
  11. Swedish Society of Medicine Funding Source: Medline
  12. Emil and Wera Cornell foundation Funding Source: Medline
  13. Diabetes Research & Wellness Foundation Funding Source: Medline
  14. the Royal Physiographic Society in Lund Funding Source: Medline
  15. The Swedish Stroke Association Funding Source: Medline
  16. Hjelt foundation Funding Source: Medline
  17. ALF Grants Region Skane, Bundy Academy Funding Source: Medline
  18. Innovative Medicines Initiative [IMI-2008/115006] Funding Source: Medline

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This study found that elevated plasma levels of sCD40 and sCD40L are associated with cardiovascular disease, with sCD40 levels correlating with the severity of carotid atherosclerosis and predicting future cardiovascular events, while intra-plaque levels are associated with a vulnerable plaque phenotype.
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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