Soluble CD40 ligand and atrial fibrillation: Relationship to platelet activation, and endothelial damage/dysfunction

Objective.There remains a need for biomarkers to guide therapy in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Our objective was to determine whether measures of platelet activation or inflammation are associated with disease activity in Wegener’s granulomatosis (WG).Methods.Study subjects were participants in a clinical trial. Soluble CD40 ligand (sCD40L), C-reactive protein, interleukin 6 (IL-6), IL-8, monocyte chemoattractant protein 1 (MCP-1), P-selectin, vascular endothelial growth factor, and proteinase 3 (PR3)-specific ANCA were measured by ELISA using plasma samples obtained at baseline (active disease), at remission, and prior to, during, and after first flares. Disease activity was assessed by the Birmingham Vasculitis Activity Score for WG (BVAS/WG). Association of biomarkers with disease activity was determined with conditional logistic and linear regression.Results.Over a mean followup of 27 months, 180 subjects underwent 2044 visits; markers were measured in 563 samples. Longitudinally, all markers other than IL-6 were associated with disease activity. The strongest associations for active disease at baseline versus remission were observed for sCD40L (OR 4.72, 95% CI 2.47–9.03), P-selectin (OR 6.26, 95% CI 2.78–14.10), PR3-ANCA (OR 9.41, 4.03–21.99), and inversely for MCP-1 (OR 0.36, 95% CI 0.22–0.57). BVAS/WG increased by 0.80 (95% CI 0.44–1.16), 0.83 (95% CI 0.42–1.25), and 0.81 (95% CI 0.48–1.15) per unit-increase in PR3-ANCA, sCD40L, and P-selectin, respectively; and decreased by 1.54 (95% CI 0.96–2.12) per unit-increase in MCP-1.Conclusion.Cytokines arising from within the circulation, including those of platelet activation, correlate with disease activity in WG.

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Association of Soluble CD40 Ligand With Duration of Atrial Fibrillation and With Intensity of Spontaneous Echocardiographic Contrast

JACC: Clinical Electrophysiology ◽

10.1016/j.jacep.2016.03.006 ◽

2016 ◽

Vol 2 (5) ◽

pp. 623-632 ◽

Cited By ~ 4

Author(s):

Kevin P. Cohoon ◽

Matylda Mazur ◽

Robert D. McBane ◽

Naser Ammash ◽

Samuel J. Asirvatham ◽

...

Keyword(s):

Atrial Fibrillation ◽

Cd40 Ligand ◽

Soluble Cd40 Ligand

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Prognostic value of plasma soluble CD40 ligand in patients with chronic non-valvular atrial fibrillation

EP Europace ◽

10.1093/europace/eum284 ◽

2008 ◽

Vol 10 (2) ◽

pp. 210-214 ◽

Cited By ~ 16

Author(s):

H. Duygu ◽

V. Barisik ◽

H. Kurt ◽

U. Turk ◽

E. Ercan ◽

...

Keyword(s):

Atrial Fibrillation ◽

Prognostic Value ◽

Cd40 Ligand ◽

Soluble Cd40 Ligand

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Internalization of IgG-Coated Targets Results in Activation and Secretion of Soluble CD40 Ligand and RANTES by Human Platelets

Clinical and Vaccine Immunology ◽

10.1128/cvi.00296-10 ◽

2010 ◽

Vol 18 (2) ◽

pp. 210-216 ◽

Cited By ~ 24

Author(s):

Adam J. Antczak ◽

Joshua A. Vieth ◽

Navinderjit Singh ◽

Randall G. Worth

Keyword(s):

Platelet Activation ◽

Cytokine Production ◽

Cd40 Ligand ◽

Human Platelets ◽

Cytochalasin D ◽

Soluble Cd40 Ligand ◽

Actin Remodeling ◽

Inflammatory Reactions ◽

Coated Particles ◽

Immunological Reactions

ABSTRACTPlatelets are crucial elements for maintenance of hemostasis. Other functions attributable to platelets are now being appreciated, such as their role in inflammatory reactions and host defense. Platelets have been reported to bind immunological stimuli like IgG complexes, and for nearly 50 years it has been speculated that platelets may participate in immunological reactions. Platelets have been reported to bind and internalize various substances, similar to other leukocytes, such as macrophages and dendritic cells. In the present study, we tested the hypothesis that human platelets can bind and internalize IgG-coated particles, similar to leukocytes. To this end, we observed that interaction with IgG-coated beads resulted in platelet activation (as measured by CD62P expression), internalization of targets, and significant soluble CD40 ligand (sCD40L) and RANTES (regulated uponactivation,normalTcellexpresses andsecreted) secretion. Blocking FcγRIIA with monoclonal antibody (MAb) IV.3 or inhibiting actin remodeling with cytochalasin D inhibited platelet activation, internalization, and cytokine production. These data suggest that platelets are capable of mediating internalization of IgG-coated particles, resulting in platelet activation and release of both sCD40L and RANTES.

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Platelet-specific markers are associated with monocyte-platelet aggregate formation and thrombin generation potential in advanced atherosclerosis

Thrombosis and Haemostasis ◽

10.1160/th15-07-0598 ◽

2016 ◽

Vol 115 (03) ◽

pp. 615-621 ◽

Cited By ~ 17

Author(s):

Cihan Ay ◽

Julia Riedl ◽

Christoph W. Kopp ◽

Beate Eichelberger ◽

Renate Koppensteiner ◽

...

Keyword(s):

Platelet Activation ◽

Thrombin Generation ◽

Thrombus Formation ◽

Cd40 Ligand ◽

Aggregate Formation ◽

Soluble Cd40 Ligand ◽

Platelet Factor ◽

Platelet Aggregate ◽

Angioplasty And Stenting

SummaryPlatelet activation and thrombin generation are crucial steps in primary and secondary haemostasis. However, both also play major roles in intravascular thrombus formation and therefore in the development of adverse cardiovascular events. In the current study, we first sought to investigate the associations of the platelet biomarkers platelet factor (PF)-4, thrombospondin (TSP)-1, soluble CD40 ligand (sCD40L), and soluble P-selectin (sP-selectin) with each other and with monocyte-platelet aggregate (MPA) formation in 316 patients undergoing angioplasty and stenting. To better understand the interplay between platelet activation and thrombin generation, we subsequently investigated the associations of the platelet biomarkers with thrombin generation potential. The mostly platelet-specific markers PF-4, TSP-1 and sCD40L correlated strongly with each other (all p < 0.001), and the best correlation was observed between PF-4 and TSP-1 (r=0.91). In contrast, sP-selectin, which derives from platelets and endothelial cells, correlated rather poorly with TSP-1 (r=0.12, p=0.04), and did not correlate with PF-4 and sCD40L. While PF-4, TSP-1 and sP-selectin correlated significantly with in vivo MPA formation (all p < 0.001), no such association was found between sCD40L and MPA formation. PF-4, TSP-1 and sCD40L correlated strongly with peak thrombin generation (all p < 0.001) with the best correlation between PF-4 and peak thrombin generation (r=0.55), whereas sP-selectin did not correlate with peak thrombin generation. Likewise, PF-4, TSP-1 and sCD40L correlated significantly with the area under the thrombin generation curve (AUC; all p< 0.01), whereas sP-selectin did not correlate with the AUC. In conclusion, platelet-specific markers are associated with MPA formation and thrombin generation potential in patients with advanced atherosclerosis.

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Increased Concentrations of Soluble CD40 Ligand, RANTES and GRO-α in Preeclampsia – Possible Role of Platelet Activation

Thrombosis and Haemostasis ◽

10.1055/s-0037-1616061 ◽

2001 ◽

Vol 86 (11) ◽

pp. 1272-1276 ◽

Cited By ~ 21

Author(s):

Nils Olav Solum ◽

Thor Ueland ◽

Vibeke Videm ◽

Pål Aukrust ◽

Jan Roar Mellembakken

Keyword(s):

Platelet Activation ◽

Inflammatory Mediators ◽

Ex Vivo ◽

Platelet Rich Plasma ◽

Cd40 Ligand ◽

Soluble Cd40 Ligand ◽

Inflammatory Reactions ◽

Free Plasma

SummaryActivated platelets may release inflammatory mediators that activate leukocytes and trigger inflammatory reactions in endothelial cells. We examined the concentrations of soluble CD40 ligand (sCD40L) and the chemokines RANTES and GRO-α in platelet-free plasma (PFP), and unstimulated and SFLLRN-stimulated platelet-rich plasma (PRP), as well as in platelet pellets before stimulation using enzyme immunoassays. Nineteen women with normal and twenty-one with preeclamptic pregnancies were studied, and several differences between these two groups of pregnancies were revealed (1). Women with preeclampsia had significantly increased concentrations of sCD40L and GRO-α in PFP (2). Platelets from these patients spontaneously released larger quantities of CD40L and RANTES ex vivo (3). When further activated ex vivo by SFLLRN, platelets from preeclamptic women released lower amounts per platelet of CD40L, RANTES and GRO-α (4). The platelet pellets in preeclamptic women contained decreased amounts of CD40L, RANTES and GRO-α per platelet. Our findings suggest enhanced platelet activation in vivo during preeclampsia resulting in increased release of inflammatory mediators, possibly contributing to inflammation, leukocyte activation and endothelial dysfunction in this disorder.

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