Differences of soluble CD40L in sera and plasma: Implications on CD40L assay as a marker of thrombotic risk

Ahn, Eugene; Lander, Gabriella; Jy, Wenche; Bidot, Carlos; Jiménez, Joaquín J.; Horstman, Lawrence L.; Ahn, Yeon S.

doi:10.1016/j.thromres.2004.06.005

Cited by 75 publications

(85 citation statements)

References 20 publications

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“…The sCD40L plasmatic values showed by HUS patients were similar to those reported in other pathological conditions such as cardiovascular diseases, diabetes, HIV infection or smokers [41,[45][46][47][48][49] and it can be considered as a marker of thrombotic risk [26]. Therefore, and based on the present results, we propose that quantification of sCD40L in plasma could be used as a surrogate and early marker of microvascular dysfunction and/or platelet activation in Stx-associated diarrheas.…”

Section: Discussionsupporting

confidence: 87%

See 1 more Smart Citation

Soluble CD40 Iigand and Oxidative Response Are Reciprocally Stimulated during Shiga Toxin-Associated Hemolytic Uremic Syndrome

Recalde¹,

Álvarez²,

Alberto³

et al. 2017

Preprint

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Shiga toxin (Stx) produced by Escherichia coli is the main pathogenic factor of diarrhea-associated hemolytic uremic syndrome (HUS), which is characterized by obstruction of renal microvasculature by platelet-fibrin thrombi. It is well known that the oxidative imbalance generated by Stx induces platelet activation, contributing to thrombus formation. Moreover, activated platelets release soluble CD40 ligand (sCD40L) which in turn contributes to oxidative imbalance, triggering the release of reactive oxidative species (ROS) on various cellular types. The aim of this work was to determine if the interaction between the oxidative response and platelet-derived sCD40L participates in the pathogenic mechanism during HUS. Activated human glomerular endothelial cells (HGEC) by Stx2 induced platelets to adhere to them.Although platelet adhesion did not contribute to endothelial damage, high levels of sCD40L were released to the medium. The release of sCD40L by activated platelets was inhibited by antioxidant treatment.Furthermore, we found increased levels of sCD40L in plasma from HUS patients, which were also able to trigger the respiratory burst in monocytes, in a sCD40L-dependent manner. Thus, we concluded that platelet-derived sCD40L and the oxidative response are reciprocally stimulated during Stx2-associated HUS.This process may contribute to the evolution of glomerular occlusion and the microangiopathic lesions.

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Section: Discussionsupporting

confidence: 87%

“…It retains the ability to activate its widely expressed receptor CD40 [21], promoting inflammatory or thrombotic response by causing further platelet activation [23]. More than 95% of circulating CD40L is derived from platelets [25,26].…”

Section: Introductionmentioning

confidence: 99%

Soluble CD40 Iigand and Oxidative Response Are Reciprocally Stimulated during Shiga Toxin-Associated Hemolytic Uremic Syndrome

Recalde¹,

Álvarez²,

Alberto³

et al. 2017

Preprint

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“…Our study is consistent with prior studies demonstrating that soluble CD40L concentrations vary by whether they are measured in serum or in plasma. 28 Prior literature on serum TNFR2 concentrations in smokers is conflicting. Soluble TNF receptors compete with membrane-bound receptors for binding tumor necrosis factor, thereby acting as inhibitors of TNF activity on tissue, though in some circumstances they can also bind circulating TNF and prolong its activity in the circulation.…”

Section: Individual Markersmentioning

confidence: 99%

Relation of smoking status to a panel of inflammatory markers: The Framingham offspring

et al. 2008

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Aims-We sought to investigate the hypothesis that smoking is accompanied by systemic inflammation.Methods and Results-We examined the relation of smoking to 11 systemic inflammatory markers in Framingham Study participants (n=2944, mean age 60 years, 55% women, 12% ethnic minorities) examined from 1998-2001. The cohort was divided into never (n=1149), former (n=1424), and current smokers with last cigarette >6 hours (n=134) or ≤6 hours (n=237) prior to phlebotomy. In multivariable-adjusted models there were significant overall between-smoking group differences (defined as p<0.0045 to account for multiple testing) for every inflammatory marker tested, except for serum CD40 ligand (CD40L), myeloperoxidase (MPO) and tumor necrosis factor receptor-2 (TNFR2). With multivariable-adjustment, pair-wise comparisons with never smokers revealed that former smokers had significantly lower concentrations of plasma CD40L (p<0.0001) and higher concentrations of C-reactive protein (p=0.002).Conclusions-As opposed to never smokers, those with acute cigarette smoke exposure (≤6 hours) had significantly higher concentrations of all markers (p<0.0001) except serum CD40L, MPO, and TNFR2; plasma CD40L were significantly lower. Compared with never smokers, cigarette smokers have significantly elevated concentrations of most circulating inflammatory markers, consistent with the hypothesis that smoking is associated with a systemic inflammatory state.

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“…The choice of serum to determine sCD40L by ELISA in this study had into consideration published data, 25,26 and exploratory analysis performed by us. Ahn et al 25 demonstrated that as long as preanalytical conditions were kept ,4…”

Section: Methodsmentioning

confidence: 99%

“…One of the sources contributing to higher serum levels is platelets, therefore, poor-platelet plasma is recommended. 25 We have performed sCD40L determinations on random blood samples (n 5 42) on both serum and poor-platelet plasma fractions. For almost 40% of the analyzed samples (n 5 15), sCD40L concentrations in poor-platelet plasma were below the detection limit of the ELISA assay, contrasting with none in serum.…”

Section: Methodsmentioning

confidence: 99%

Changes of soluble CD40 ligand in the progression of acute myocardial infarction associate to endothelial nitric oxide synthase polymorphisms and vascular endothelial growth factor but not to platelet CD62P expression

Napoleão

Monteiro

Cabral

et al. 2015

Translational Research

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Abbreviations: AMI ¼ acute myocardial infarction; APC ¼ allophycocyanin; Asp ¼ aspartate; cTNT ¼ cardiac troponin; CAD ¼ coronary artery disease; CRP ¼ C-reactive protein; CK ¼ creatine kinase; eNOS ¼ endothelial nitric oxide synthase; ELISA ¼ enzyme-linked immunosorbent assay; FITC ¼ fluorescein isothiocyanate; FAU ¼ fluorescence arbitrary units; Glu ¼ glutamic acid; LME ¼ linear mixed effects model; MPs ¼ microparticles; NO ¼ nitric oxide; NT-proBNP ¼ N-terminal pro-brain natriuretic peptide; PCI ¼ percutaneous coronary intervention; PBS ¼ phosphate-buffered saline; PE ¼ Phycoerythrin; CD62P ¼ P-selectin; sCD40L ¼ soluble CD40 ligand; SA ¼ stable angina pectoris; VEGF ¼ vascular endothelial growth factor INTRODUCTION CD40L is a signaling molecule, 1-3 implicated in thrombosis and inflammatory response to vascular injury. [4][5][6] The relationship of CD40L with coronary artery disease (CAD) has been established, 2,7-9 as also its implication in endothelial dysfunction. [10][11][12][13][14] However, whether the soluble CD40 ligand (sCD40L) could also influence endothelial dysfunction after acute myocardial infarction (AMI) injury remains unclear.In vitro studies have shown that sCD40L inhibits angiogenesis and also growth factor-induced human umbilical vein endothelial cell migration, which is achieved by generation of free radicals and inhibition of nitric oxide (NO) production. 10 The authors hypothesized that the sCD40L could inhibit reendothelialization of an injured vessel, thereby affecting the restenosis. 10Research efforts have been directed toward the finding of biomarkers to assess endothelial function and its correlation with AMI. Genetic indicators, such as the polymorphisms of endothelial NO synthase (eNOS) gene, 15,16 may provide insight into endothelial cells function.Vascular endothelial growth factor (VEGF) is a wellknown promoter of angiogenesis and an endogenous regulator of endothelial integrity. [17][18][19] The prognostic information provided by VEGF independently of other markers likely points toward an important role for angiogenesis in regulating myocardial repair and reperfusion after AMI. 17,20 Current opinion suggests a differential role of CD40L (both soluble and membrane-bound forms, which includes microparticles in circulation) 21 at different stages of CAD, contrasting with the traditional view of an unvarying function of the CD40L-CD40-sCD40L system interactions in the disease. 6 In that perspective, no clear indication of the interplay of CD40L with endothelial and vascular function markers and their importance in the pathophysiology of the AMI has been obtained so far in human clinical studies. Therefore, the aim of this study was to evaluate the relationship of sCD40L with markers of platelet activation, endothelial and vascular function during an early recovery period after AMI. To achieve this goal, the time changes over 1 month of sCD40L levels were assessed in AMI patients and correlated with the CD40L expressed on platelets and microparticles, CD62P expression on platele...

show abstract

Differences of soluble CD40L in sera and plasma: Implications on CD40L assay as a marker of thrombotic risk

Cited by 75 publications

References 20 publications

Soluble CD40 Iigand and Oxidative Response Are Reciprocally Stimulated during Shiga Toxin-Associated Hemolytic Uremic Syndrome

Soluble CD40 Iigand and Oxidative Response Are Reciprocally Stimulated during Shiga Toxin-Associated Hemolytic Uremic Syndrome

Relation of smoking status to a panel of inflammatory markers: The Framingham offspring

Changes of soluble CD40 ligand in the progression of acute myocardial infarction associate to endothelial nitric oxide synthase polymorphisms and vascular endothelial growth factor but not to platelet CD62P expression

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