Elevations in soluble CD40 ligand in patients with high platelet aggregability undergoing percutaneous coronary intervention

Abstract

High aggregatory responses despite antiplatelet treatment is associated with an increased risk of thrombotic complications following percutaneous coronary intervention (PCI). In the present study, we investigated the relationship between platelet aggregatory responses to ADP and the release of CD40L (sCD40L): an immunomodulatory compound involved in atherothrombosis - in patients undergoing PCI. ADP-induced platelet aggregation, sCD40L and soluble P-selectin (sP-selectin) were determined before and 24 h after PCI, in samples from 52 patients receiving aspirin and thienopyridines. Platelet aggregation to ADP above the median was defined as 'high aggregation', and aggregation below the median as 'low aggregation'. Data below are medians and interquartile ranges. Patients with 'high platelet aggregability' had a significantly higher increase in both sCD40L (Delta-values: 0.78 (-0.19-3.18) vs. -0.65 (-2.10-0.00) ng/ml, P = 0.002) and sP-selectin (Delta-values: 8.0 (-2.00-16.00) vs. 4.50 (-13.00-0.50) ng/ml, P = 0.001) compared with patients with 'low platelet aggregability'. In a multivariate linear regression analysis adjusted for clinical characteristics and type of preintervention therapy, the only independent predictors of sCD40L and sP-selectin were platelet aggregation to ADP before PCI (P < 0.001) and the combination of platelet aggregation to ADP before PCI and urgency of PCI (P < 0.001). Circulating CD40L is more markedly increased after PCI in patients with high ADP-induced platelet aggregation.

Men with Lower HDL Cholesterol Levels have Significant Increment of Soluble CD40 Ligand and High-sensitivity CRP Levels Following the Cessation of Long-term Clopidogrel Therapy

“…Soluble CD40L is a marker of platelet activation, and the majority of sCD40L in the blood is derived from activated platelets 23,24) . It has also been demonstrated that a higher degree of platelet aggregation prior to angioplasty is associated with a greater increase in sCD40L release into the circulation after the procedure 25) . In this study, we observed a statistically significant increase in the sCD40L levels following the cessation of clopidogrel in relation to the values obtained under treatment with clopidogrel.…”

Monocyte CD40 expression in young healthy female smokers and/or oral contraceptives users without additional risk factors for atherosclerosis

“…The expression of CD40/CD40L system in monocytes and their activation status in atherosclerosis and cardiovascular events are closely related to each other [6][7][8][9][10]. In this prospective, case-control study of Fig.…”

“…Rapid up-regulation of CD154 on activated platelets leads to the release of soluble CD154 (sCD40L) and inflammatory response in cells constitutively expressing CD40 [9]. Accordingly, increased platelet activation and elevated levels of CD154 were shown in patients with acute cerebral symptoms, myocardial infarction, and hypercholesterolemic subjects [7][8][9][10][11]. Healthy women with increased plasma levels of soluble CD40L were shown to be at risk for cardiovascular events [12].…”

“…It had been originally identified on B lymphocytes, and was later found to be expressed constitutively on monocytes/ macrophages, smooth muscle cells, and endothelial cells [9]. Activation of CD40 by its ligand CD154 triggers the release of proinflammatory cytokines, adhesion receptors, tissue factor, metalloproteinases and prostaglandins [7][8][9]. CD154 is a transmembrane protein …”

“…Moreover, elevated levels of inflammatory cytokines and adhesion molecules have been shown in patients with CVD [7,8]. One of the potent immune mediators involved in atherothrombosis is CD40, and its counterpart CD40 ligand (CD40L, CD154) [9].…”