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

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.

Vascular endothelium and inflammatory process, in patients with combined Type 2 diabetes mellitus and coronary atherosclerosis: the effects of vitamin C.

AIMS: Type 2 diabetes mellitus (DM) and coronary artery disease (CAD) are both associated with endothelial dysfunction and elevated oxidative and inflammatory state. We examined the effect of vitamin C on endothelial function and levels of soluble vascular cell adhesion molecule (sVCAM-1), interleukin-6 (IL-6) and tumour necrosis factor (TNF-alpha), in DM patients with or without CAD and in non-diabetic subjects. METHODS: Thirty-seven patients with DM + CAD, 17 patients with DM without CAD and 21 non-diabetic subjects were divided into groups receiving vitamin C 2 g/day or no anti-oxidant for 4 weeks. Forearm blood flow was determined using venous occlusion gauge-strain plethysmography. Forearm vasodilatory response to reactive hyperemia was considered as index of endothelium-dependent dilation. RESULTS: Baseline levels of IL-6 and TNF-alpha were significantly higher in patients with DM + CAD compared with patients with DM (P < 0.01) or non-diabetic subjects (P < 0.01). IL-6 and TNF-alpha levels were also higher in DM compared with non-diabetic subjects (P < 0.05). sVCAM-1 levels were lower in non-diabetic controls compared with DM + CAD (P < 0.05) or DM (P < 0.05). Reactive hyperaemia was higher in non-diabetic controls compared with DM + CAD (P < 0.001) or DM (P < 0.001). Vitamin C significantly increased reactive hyperaemia only in the DM + CAD group, while it had no effect on serum levels of sVCAM-1, TNF-alpha and IL-6 in any of the groups. CONCLUSIONS: Type 2 diabetes mellitus is associated with impaired endothelial function and increased levels of TNF-alpha, IL-6 and sVCAM-1, especially in patients with DM and CAD. Vitamin C significantly increased forearm vasodilatory response to reactive hyperaemia only in patients with combined DM and CAD.