The Role of Osteoprotegrin/Nuclear Factor kB Ligand in Coronary Collateral Development

Abstract

Osteoprotegrin (OPG), as a member of the TNF family is demonstrated to be a potential regulator of the endothelial function and angiogenesis by neutralization of nuclear factor kB ligand (RANKL). We investigated the OPG and RANKL gene expressions in circulating peripheral blood mononuclear cells (PBMCs) of Coronary artery disease (CAD) patients with different extents of coronary collateral development. In a cross-sectional study, 206 individuals with angiographically documented CAD were recruited. Severity of CAD was defined by the number of involved coronary vessels. The Rentrop scoring system was used to grade the extent of collateral development. Grade 0 or 1 collateralization was considered poor collateralization. RNA extraction and cDNA synthesis were performed. OPG and RANKL gene expressions were evaluated using quantitative real-time PCR. Among patients with CAD, 48.5% (100), 16.5%(34) and 35%(72) were considered to have one to three degrees of coronary artery involvement, respectively. The OPG and the ratio of OPG to RANKL expression were significantly elevated in patients with well-developed collateralization. In a logistic regression, severity of CAD was associated with a better collateral development, and OPG gene over expression was correlated with a better collateralization, independently of other variables. In conclusion, it seems that OPG might have an important role in prognosis of CAD; its up-regulation is parallel with CAD severity while it can enhance collateral development.