Relationship between serum RANKL/osteoprotegerin complex and endothelial progenitor cells in ischemic chronic heart failure

Abstract

The objective of this study was to assess an interrelationship serum RANKL/OPG complex with counts of circulating proangiogenic endothelial progenitor cells (EPCs) labeled as CD14⁺CD309⁺, and CD14⁺CD309⁺Tie2⁺ in patients with ischemic chronic heart failure (CHF).

Methods: The study retrospectively evolved 153 patients (86 males) aged 48 to 62 years with angiographically documented stable coronary artery disease (CAD). One hundred nine patients (71.2%) had systolic or diastolic CHF. The control group consisted of 25 healthy volunteers with matching age, sex, and body mass index. Serum RANKL (sRANKL) and OPG were measured by high-sensitive ELISA at baseline. EPC populations were phenotyped by flow cytofluorimetry per High-Definition Fluorescence Activated Cell Sorter methodology.

Results: Numerous of EPCs with phenotypes of CD14⁺CD309⁺ and CD14⁺CD309⁺Tie²⁺ were significantly lower in CAD patients when compared with healthy subjects. There is a significant trend to decrease of EPC numerous depending presence of CHF. The sRANKL level, OPG level, and sRANKL / OPG ratio were significantly higher in CHF subjects as compared to those without CHF (P=0.001). On multivariate analysis, CHF, sRANKL/OPG ratio, OPG, and NT-pro-BNP remained as independent predictors of decreased EPCs with phenotypes of CD14⁺CD309⁺ and CD14⁺CD309⁺Tie²⁺. Using reclassification methods, we found that the addition of sRANKL/OPG ratio to the ABC standard model (CHF) improved the relative integrated discrimination indices by 12.5% for CD14⁺CD309⁺ depletion, by 17.3% for CD14⁺CD309⁺Tie²⁺depletion.

Conclusion: We found that sRANKL/OPG ratio remained statistically significant predictor for depletion of proangiogenic EPCs in CAD patients