Serum levels of TRAIL OPG and RANKL in patients with severe heart failure

Background Inflammation and apoptosis are associated with the progressive deterioration of left ventricular function. Osteoprotegerin (OPG) is a soluble member of the TNF receptor superfamily The activity best characterized for OPG is inhibition of receptor activator of nuclear factor-kappa B ligand (RANKL). OPG can also interact with TNF-related apoptosis-inducing ligand (TRAIL). OPG may exert direct biological activities independent of its neutralizing effect towards TRAIL and RANKL. The physiologic role of TRAIL may be tissue specific and more complex than initially assumed. TRAIL - mediated apoptosis may be involved in cardiomyocyte apoptosis in chronic heart failure. Both soluble RANKL and OPG may induce the activation of matrix metalloproteinases (MMPs) involved in ventricular remodeling. TRAIL has also endothelial protective properties. The role of the interaction between OPG and TRAIL with potential antiapoptotic effects has not been well studied. The objective of the study was to investigate the relationship between OPG, RANKL and TRAIL in patients with ischemic cardiomyopathy and chronic heart failure. Material and methods. In 23 patients with ischemic cardiomyopathy and severe heart failure (NYHA III and IV LVEF = 0.25 +/- 0.1), 10 patients with Killip II class acute myocardial infarction (AMI), and II controls (healthy volunteers) we measured TRAIL (ELISA assay), OPG (ELISA assay), RANKL (ELISA assay), NT proBNP (ELISA assay). Values (pg/ml) are expressed as mean +/- SEM Results. As compared with controls, in patients with ischemic cardiomyopathy serum levels of TRAIL are significantly decreased (82.6 +/- 7.53 pg/ml vs 103 +/- 7.98; p < 0.05), while serum levels of OPG are increased in both groups (in ischemic cariomyopathy: 137.74 +/- 19.81 pg/ml vs. 60.18 +/- 5.06; p < 0.006; in AMI: 129.8 +/- 20.2 pg/ml vs. 60.18 +/- 5.06; p < 0.0008). No differences in serum levels of OPG, RANKL and TRAIL were found between the two study groups. Positive correlations between serum levels of OPG and the age of the patients, and negative correlations between serum levels of TRAIL and OPG (r = - 0.574; p < 0.01) and serum levels of TRAIL and RANKL (r = - 0.458; p < 0.05) were found. Conclusions. In patients with heart failure in the same etiological context, ischemic cardiomyopathy and acute myocardial infarction, the patterns of TRAIL, OPG and RANKL serum levels are different. No correlations between serum levels of TRAIL, OPG and RANKL or with the LVEF were found.