Soluble CD40 Ligand in Acute Coronary Syndromes

Heeschen, Christopher; Dimmeler, Stefanie; Hamm, Christian W.; Brand, Marcel J. van den; Boersma, Eric; Zeiher, Andreas M.; Simoons, Maarten L.

doi:10.1056/nejmoa022600

Cited by 765 publications

(433 citation statements)

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“…In the latter case, activated platelets expressing or releasing CD40L [22,24] could also interact with CD40 on duct cells, since islet cell suspensions are directly injected into the portal vein. CD40-CD40L interactions at the pancreatic duct cell level could therefore contribute to beta cell damage in Type 1 diabetes and after islet transplantation.…”

Section: Discussionmentioning

confidence: 99%

“…The ligand for CD40 (CD40L) is a type II transmembrane protein expressed on stimulated T cells but also on mast cells, basophils and platelets. A soluble form of CD40L is released from activated platelets or shed from stimulated lymphocytes [21,22,23,24]. CD40-CD154 interactions were shown to play a pivotal role in different T-cell-mediated inflammatory disorders [20,21,25,26,27] and disruption of CD40-CD40L interactions proved to be sufficient to prevent the development and progression of several autoimmune diseases [28,29] as well as allograft rejection [21,26].…”

Section: Introductionmentioning

confidence: 99%

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CD40 expression on human pancreatic duct cells: role in nuclear factor-kappa B activation and production of pro-inflammatory cytokines

Vosters

Beuneu

Nagy³

et al. 2004

Diabetologia

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Aims/hypothesis. Human pancreatic duct cells are closely associated with islet beta cells, and contaminate islet suspensions transplanted in Type 1 diabetes mellitus patients. Activated duct cells produce cytotoxic mediators and possibly contribute to the pathogenesis of Type 1 diabetes mellitus or islet graft rejection. As CD40 transduces activation signals involved in inflammatory and immune disorders, we investigated CD40 expression on duct cells and their response to CD40 engagement. Methods. CD40 expression on human pancreatic duct cells was analysed by flow cytometry and immunohistochemical analyses. To assess the function of CD40 expression on duct cells, activation of the transcription factor nuclear factor-kappa B was determined using electrophoretic mobility shift assay and ELISA. Cytokine mRNA levels were quantified by real-time RT-PCR, and protein levels by Luminex technology. Results. Isolated human pancreatic duct cells and Capan-2 cell lines were found to express constitutively CD40. The expression of CD40 on duct cells was confirmed in vivo on human normal and pathological pancreatic specimens. CD40 ligation on Capan-2 cells induced rapid nuclear factor-kappa B activation, and supershift assays demonstrated that p50/p65 heterodimers and p50/p50 homodimers were present in the activated complexes in the nucleus. This activation was accompanied by tumour necrosis factor-α and interleukin-1β mRNA accumulation. Tumour necrosis factor-α protein secretion was confirmed in CD40-activated Capan-2 cells and in isolated human pancreatic duct cells. Conclusions/interpretation. Interaction between activated T lymphocytes expressing CD40 ligand and duct cells expressing CD40 may contribute to the immune responses involved in Type 1 diabetes mellitus and islet graft rejection. Interfering with CD40-mediated duct cell activation could alleviate beta cell damage of immune origin.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CD40 expression on human pancreatic duct cells: role in nuclear factor-kappa B activation and production of pro-inflammatory cytokines

Vosters

Beuneu

Nagy³

et al. 2004

Diabetologia

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“…24 Nevertheless, it may be a partly useful marker in some subjects with high cardiovascular risks, such as unstable plaque 25 or acute coronary syndromes. 9 Large studies performed in the healthy general population have reported that circulating sCD40L is not useful in screening for subclinical atherosclerosis 26 and is poorly associated with known cardiovascular risk factors. 27 Likewise, our findings showed the inverse association between CPT%PDV and sCD40L in some patients, including males and smokers.…”

Section: Discussionmentioning

confidence: 99%

“…8 Several studies demonstrate that plasma C-reactive protein (CRP), adipocytokines and soluble CD40 ligand (sCD40L) act as atherosclerotic biomarkers and are independently associated with cardiovascular events. 7,9,10 Development in ultrasound technology has made it possible to assess blood flow in the distal left anterior descending coronary artery (LAD) with transthoracic Doppler echocardiography (TTE). 11 The cold pressor test (CPT) is one of the methods used to estimate coronary endothelial function or early atherosclerosis.…”

Section: Introductionmentioning

confidence: 99%

Change of Coronary Flow Velocity During the Cold Pressor Test Is Related to Endothelial Markers in Subjects With Chest Pain and a Normal Coronary Angiogram

Hwang

Youn

Lee

et al. 2011

Clinical Cardiology

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Background: Several studies demonstrated that endothelial or atherosclerotic biomarkers, including plasma free insulin-like growth factor-I(IGF-I), soluble CD40 ligand (sCD40L), adiponectin, and leptin have an influence on coronary endothelial function. Hypothesis: The aim of the present study was to investigate whether change of coronary flow velocity of the distal left anterior descending artery (LAD) during the cold pressor test (CPT) with transthoracic Doppler echocardiography (TTE) was associated with these biomarkers in subjects with chest pain and a normal coronary angiogram. Methods: In 190 subjects (mean age, 54 ± 11 years; male:female, 113:77) with chest pain and a normal coronary angiogram, peak diastolic velocity (PDV) of the distal LAD during the CPT with TTE was assessed. Acetylcholine provocation test was performed in 58 subjects (mean age, 51 ± 10 years) who were clinically suspected of vasospasm. CPT%PDV was defined as the percent change in PDV during the CPT. Associations between CPT%PDV and clinical parameters were analyzed. Results: According to multiple regression analysis, CPT%PDV was associated with plasma free IGF-I in the entire study population (β = 0.295, P < 0.001 in all subjects; β = 0.341, P = 0.001 in males; β = 0.243, P = 0.037 in females; β = 0.303, P = 0.002 in nonsmokers; and β = 0.256, P = 0.047 in smokers), and sCD40L in males (β = −0.269, P = 0.008)and smokers (β = −0.261, P = 0.046). Subjects with vasospasm to intracoronary acetylcholine had lower plasma free IGF-I(6.9 ± 3.3 vs 8.9 ± 3.4, P = 0.026) and CPT%PDV (8.8 ± 24.9 vs 52.7 ± 26.0, P < 0.001) than the others. Plasma adiponectin and leptin were not associated with CPT%PDV. Conclusions: Change of coronary flow velocity assessed using the CPT with TTE may be related to endothelial markers, especially plasma free IGF-I.

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“…Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. (3,8,9). CD40L also plays a role in thrombosis by inducing TF expression on endothelial cells and monocytes, operating as a platelet agonist, and stabilizing arterial thrombi (1,3,8,10).…”

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confidence: 99%

Developmental Changes in Soluble CD40 Ligand

Cholette¹,

Blumberg²,

Phipps³

et al. 2008

The Journal of Pediatrics

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Objectives-To determine if soluble CD40 ligand (sCD40L; formally CD154) levels vary with age and to identify age-dependent ranges in healthy pediatric and adult populations.Study design-sCD40L was measured in 25 neonates, 74 children (3 months -15 years) and 20 adults using an enzyme-linked immunosorbent assay. For age group comparisons, Mann-Whitney tests were performed. Correlation coefficients assessed relationships between plasma and serum sCD40L.Results-Plasma sCD40L levels were higher in neonates than in all other age groups, (p<0.001). All grouped pediatric plasma levels were significantly higher than in adults (p<0.0001). There were no significant differences in plasma sCD40L between pediatric age groups. Serum levels were significantly higher in neonates than in any other age group (p <0.0001). Pediatric and adult serum sCD40L levels were not significantly different.Conclusions-Plasma sCD40L levels are highest at birth and remain higher than those in adults throughout childhood. Reasons for such developmental changes remain to be investigated. Age appropriate reference ranges should be used when sCD40L is being evaluated in pediatric disorders. Keywords platelets; platelet activation; pediatric; reference valuesOriginally identified on B lymphocytes, CD40 is a membrane receptor protein belonging to the tumor necrosis factor (TNF) receptor family (1,2,3). Its ligand, CD40L (formally CD154), is a TNF family trimeric transmembrane protein that was initially discovered on cells of the immune system (3,4). Both CD40 and CD40L have been identified on macrophages, endothelial cells, vascular smooth muscle, fibroblasts, and most notably, platelets (3,4,5,6,7).When platelets are activated, CD40L moves from intracellular sites to the platelet surface (1,3,4). Membrane CD40L may then be cleaved, producing a soluble trimeric fragment known as sCD40L. Over 95% of circulating CD40L derives from platelets, suggesting that these cells contribute substantially to the biological functions initiated by CD40L (1,3). Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. (3,8,9). CD40L also plays a role in thrombosis by inducing TF expression on endothelial cells and monocytes, operating as a platelet agonist, and stabilizing arterial thrombi (1,3,8,10). Notably, these functions are not mediated exclusively via CD40L-CD40 interactions, because the integrin receptors αIIb βIII and α5β1 have also been found to bind CD40L (10,11). NIH Public AccessGiven the involvement in inflammation and thrombosis, it is not surprising that CD40L has been implicated in the pathophysiology of many di...

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Soluble CD40 Ligand in Acute Coronary Syndromes

Cited by 765 publications

References 38 publications

CD40 expression on human pancreatic duct cells: role in nuclear factor-kappa B activation and production of pro-inflammatory cytokines

CD40 expression on human pancreatic duct cells: role in nuclear factor-kappa B activation and production of pro-inflammatory cytokines

Change of Coronary Flow Velocity During the Cold Pressor Test Is Related to Endothelial Markers in Subjects With Chest Pain and a Normal Coronary Angiogram

Developmental Changes in Soluble CD40 Ligand

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