Levels of circulating CXCR4-positive cells are decreased and negatively correlated with risk factors in cardiac transplant recipients

Abstract

The association between levels of circulating endothelial progenitor cells (EPCs) and heart transplant recipients (HTX) with cardiac allograft vasculopathy (CAV) is under debate. The chemokine receptor CXCR4 plays an important role in the mobilization of progenitor cells and is implicated in pathological conditions, including cardiovascular disease. This study aims to evaluate the association between EPCs and CXCR4-positive cells in HTX patients. Peripheral blood mononuclear cells (PBMCs) from 34 HTX patients and 25 control participants were analyzed by flow cytometry for CXCR4-positive cells and EPCs. Endothelial progenitor cells were defined by the expression of a range of hematopoietic and endothelial lineage markers in different combinations. The ability to form endothelial cell colonies in vitro was also assessed by colony-forming unit (CFU) assay. Phenotypic analysis of EPCs by flow cytometry revealed similar levels in HTX patients compared to controls. In addition, no difference was observed between levels of EPCs or CFU number in patients with and without CAV. By contrast, CFU assay revealed a reduced number of CFUs in HTX patients compared to controls (3.3% ± 0.95 and 13.3% ± 4.5%, respectively, P = 0.014). Likewise, levels of CXCR4-positive cells were significantly reduced (15.9 ± 1.4 in patients vs 24.8 ± 3.3% in controls, P < 0.01), negatively correlated with Framingham risk score (rho = -0.4, P = 0.02) and the number of risk factors (rho = -0.3, P = 0.049). Levels of CXCR4-positive cells were also correlated with CFU number (r = 0.65, P = 0.0005). These findings further develop our understanding of the role of EPCs and endothelial CFUs in cardiovascular disease, in addition to highlighting the potential importance of CXCR4 in heart transplantation.