Interaction between cytokines and sCD40L in patients with stable and unstable coronary syndromes.
Tousoulis D., Antoniades C., Nikolopoulou A., Koniari K., Vasiliadou C., Marinou K., Koumallos N., Papageorgiou N., Stefanadi E., Siasos G., Stefanadis C.
BACKGROUND: Evidence suggests that soluble CD40-ligand (sCD40L) is elevated in coronary artery disease (CAD) and is released from activated platelets during the acute myocardial infarction (AMI). Although sCD40L is part of immune response, the mechanisms regulating its release in different disease states remain unknown. MATERIALS AND METHODS: This study enrolled 596 subjects: 201 patients with stable CAD, 109 patients with AMI and 286 healthy controls. Circulating levels of sCD40L, interleukin-6 (IL-6), soluble vascular cell adhesion molecule-a (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Patients with AMI (n = 109) had higher levels of sCD40L and IL-6 compared to both CAD (n = 201) (P < 0.01) and controls (n = 286) (P < 0.01), while CAD also had higher levels of sCD40L and IL-6 compared to controls (P < 0.01). Similarly, sICAM-1 and sVCAM-1 levels were higher in CAD and AMI compared to controls (P < 0.05). IL-6 was the only parameter independently associated with sCD40L in healthy individuals [beta (SE):0.491(0.096), P = 0.0001]. However, in CAD or AMI, only diabetes mellitus [beta (SE): 2.689 (1.082), P = 0.044 and beta (SE): 10.406 (3.215), P = 0.002, respectively] and smoking [beta (SE): 3.470 (1.111), P = 0.002 and beta (SE): 9.694 (2.478), P = 0.0001, respectively] (but not IL-6), were independently associated with sCD40L levels. CONCLUSIONS: Both CAD and AMI are accompanied by increased levels of sCD40L in parallel with an elevation of proinflammatory cytokine IL-6 and adhesion molecules sVCAM-1 and sICAM-1. Diabetes mellitus and smoking (but not IL-6 or adhesion molecules) were the only factors independently associated with sCD40L levels in CAD and AMI patients.