Interaction between cytokines and sCD40L in patients with stable and unstable coronary syndromes

Tousoulis, Dimitris; Antoniades, Charalambos; Nikolopoulou, Aggeliki; Koniari, Katerina; Vasiliadou, Carmen; Marinou, Kyriakoula; Koumallos, Nikolaos; Papageorgiou, Nikolaos S.; Stefanadi, Elli; Siasos, Gerasimos; Stefanadis, Christodoulos

doi:10.1111/j.1365-2362.2007.01834.x

Cited by 61 publications

(45 citation statements)

References 42 publications

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“…The 2 inflammatory markers, log(CRP) and sICAM-1, were weakly related to each other (rϭ0.34, Pϭ0.001) but not to log(sCD40L) (log[CRP], rϭ0.12, Pϭ0.3; sICAM-1, rϭϪ0.17, Pϭ0.2), a finding compatible with our previous observation that sCD40L is a marker of platelet activation rather than a systemic inflammatory marker in patients with advanced atherosclerosis. 16 Importantly, we found no significant association between preoperative CRP levels and the development of postoperative AF (median and 25th to 75th percentile range, 1.18 and 0.53 to 2.73 mg/mL in those who developed AF vs 1.15 and 0.63 to 3.18 mg/mL in those who remained in sinus rhythm, with OR and 95% CI per unit of log[CRP]ϭ1.00 and 0.65 to 1.53, respectively, Pϭ0.9). Similarly, preoperative levels of sICAM-1 were similar between those who developed postoperative AF (median and 25th to 75th percentile, 324 and 217 to 468 ng/mL) and those who remained in sinus rhythm (median and 25th to 75th percentile, 298 and 225 to 514 ng/mL, with ORϭ1.00, 95% CIϭ1.00 to 1.01 per unit of sICAM-1, Pϭ0.7).…”

Section: Preoperative Scd40l and Markers Of Systemic Inflammationmentioning

confidence: 99%

Preoperative sCD40L Levels Predict Risk of Atrial Fibrillation After Off-Pump Coronary Artery Bypass Graft Surgery

Antoniades

Van-Assche²,

Shirodaria³

et al. 2009

Circulation

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Background-The risk of atrial fibrillation (AF) after coronary bypass surgery has been related to redox state, inflammation, and ischemia. Platelet activation is common to all of these pathways. We investigated the relation between AF and preoperative soluble CD40 ligand (sCD40L), a proinflammatory marker released by activated platelets. Furthermore, we studied the role of inflammation, endothelial function, and redox state in this relation. Methods and Results-sCD40L levels were measured in 144 patients in sinus rhythm the day before off-pump coronary artery surgery. Systemic inflammation was assessed from levels of C-reactive protein and soluble intercellular adhesion molecule-1, and endothelial function was assessed from the brachial artery flow-mediated dilatation response. Graft samples were collected during surgery to assess vascular redox state. AF occurred in 33% of patients after surgery, with 3% still in AF after 6 weeks. Preoperative sCD40L levels were significantly higher in those who developed in-hospital AF (odds ratio for a 1-SD increase in log[sCD40L]ϭ1.97; 95% CI, 1.21 to 3.22; Pϭ0.007; after adjustment for age, sex, Euroscore, and total duration of operation). sCD40L and vascular superoxide levels were higher in patients still in AF at 6 weeks, and endothelial function was lower, although the small number of events precluded statistical analysis in this group. Systemic endothelial function, redox state, and preoperative markers of systemic inflammation were not associated with in-hospital postoperative AF. Conclusions-Preoperative platelet activation, as assessed by sCD40L levels, is a novel predictor of postoperative AF, independent of systemic endothelial function, vascular redox state, and systemic inflammation. (Circulation. 2009; 120[suppl 1]:S170-S176.)

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Section: Preoperative Scd40l and Markers Of Systemic Inflammationmentioning

confidence: 99%

Preoperative sCD40L Levels Predict Risk of Atrial Fibrillation After Off-Pump Coronary Artery Bypass Graft Surgery

Antoniades

Van-Assche²,

Shirodaria³

et al. 2009

Circulation

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“…Augmented local thrombin production in myocardial infarction patients with glucose Ͼ7.0 mmol/l was accompanied by increased platelet activation, reflected by elevated sCD40L levels in venous plasma and bleeding time blood. Of several soluble platelet activation markers, including ␤-thromboglobulin or P-selectin, sCD40L has been extensively studied in hyperglycemic subjects (8,9,21) and measured at the site of injury (19,22); ϳ95% of circulating sCD40L is plateletderived (11,23). For these reasons, sCD40L was chosen as the platelet activation marker in the current study.…”

Section: Short-term Outcomesmentioning

confidence: 99%

Hyperglycemia Is Associated With Enhanced Thrombin Formation, Platelet Activation, and Fibrin Clot Resistance to Lysis in Patients With Acute Coronary Syndrome

et al. 2008

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OBJECTIVE -Acute hyperglycemia on admission for acute coronary syndrome worsens the prognosis in patients with and without known diabetes. Postulated mechanisms of this observation include prothrombotic effects. The aim of this study was to evaluate the effect of elevated glucose levels on blood clotting in acute coronary syndrome patients.RESEARCH DESIGN AND METHODS -We studied 60 acute coronary syndrome patients within the first 12 h after pain onset, including 20 subjects with type 2 diabetes, 20 subjects with no diagnosed diabetes but with glucose levels Ͼ7.0 mmol/l, and 20 subjects with glucose levels Ͻ7.0 mmol/l. We determined generation of thrombin-antithrombin complexes (TATs) and soluble CD40 ligand (sCD40L), a platelet activation marker, at the site of microvascular injury, together with ex vivo plasma fibrin clot permeability and lysis time.RESULTS -The acute coronary syndrome patients with no prior diabetes but elevated glucose levels had increased maximum rates of formation and total production of TATs (by 42.9%, P Ͻ 0.0001, and by 25%, P Ͻ 0.0001, respectively) as well as sCD40L release (by 16.2%, P ϭ 0.0011, and by 16.3%, P Ͻ 0.0001, respectively) compared with those with normoglycemia, whereas diabetic patients had the highest values of TATs and sCD40L variables (P Ͻ 0.0001 for all comparisons). Patients with hyperglycemia, with no previously diagnosed diabetes, had longer clot lysis time (by ϳ18%, P Ͻ 0.0001) similar to that in diabetic subjects, but not lower clot permeability compared with that in normoglycemic subjects.CONCLUSIONS -Hyperglycemia in acute coronary syndrome is associated with enhanced local thrombin generation and platelet activation, as well as unfavorably altered clot features in patients with and without a previous history of diabetes.

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“…Interestingly, T2DM is independently associated with elevated sCD40L levels in patients suffering from acute coronary syndromes and myocardial infarction. 49,50 In T1DM, sCD40L levels have been shown to correlate with endothelial dysfunction, monocyte activation and increased numbers of platelet-leukocyte aggregates. 50,51 Although elevated levels of sCD40L were associated with carotid atherosclerosis in T1DM, elevated levels did not predict cardiovascular mortality.…”

Section: Do Scd40l Levels Reflect the Inflammatory Status In T2dm Patmentioning

confidence: 99%

CD40–CD40L: Linking pancreatic, adipose tissue and vascular inflammation in type 2 diabetes and its complications

Seijkens

Kusters

Engel

et al. 2012

Diabetes and Vascular Disease Research

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Numerous epidemiological studies have consistently demonstrated the strong association between type 2 diabetes mellitus (T2DM) and an increased risk to develop cardiovascular disease. The pathogenesis of T2DM and its complications are characterized by pancreatic, adipose tissue and vascular inflammation. CD40 and CD40L, members of the tumour necrosis factor (receptor) TNF(R) family, are well known for their role in immunity and inflammation. Here we give an overview on the role of CD40-CD40L interactions in the pathogenesis of T2DM with a special focus on pancreatic, adipose tissue and vascular inflammation. In addition, we explore the role of soluble CD40L (sCD40L) as a potential biomarker for the development of cardiovascular disease in T2DM subjects. Finally, the therapeutic potential of CD40-CD40L inhibition in T2DM is highlighted.

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Interaction between cytokines and sCD40L in patients with stable and unstable coronary syndromes

Cited by 61 publications

References 42 publications

Preoperative sCD40L Levels Predict Risk of Atrial Fibrillation After Off-Pump Coronary Artery Bypass Graft Surgery

Preoperative sCD40L Levels Predict Risk of Atrial Fibrillation After Off-Pump Coronary Artery Bypass Graft Surgery

Hyperglycemia Is Associated With Enhanced Thrombin Formation, Platelet Activation, and Fibrin Clot Resistance to Lysis in Patients With Acute Coronary Syndrome

CD40–CD40L: Linking pancreatic, adipose tissue and vascular inflammation in type 2 diabetes and its complications

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