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.

Neural stem/progenitor cells circulating in peripheral blood of patients with neovascular form of AMD: a novel view on pathophysiology

“…The diminished CXCR4 + Lin – CD45 - cell numbers in these patients might well have resulted from a gradual collapse of the supply of this cell population during the course of chronic vascular impairment. In support of this notion, reduced levels of circulating CXCR4-positive cells have previously been reported in diabetes and cardiovascular disease, as well as in cardiac transplant recipients [20–22]. In addition, recently published reports indicated that the number of circulating SPCs steadily decreases with the increasing age of individuals [23].…”

Fluorescence detection, enumeration and characterization of single circulating cellsin vivo: technology, applications and future prospects

“…Many areas of basic biology and pre-clinical research involve circulating cells in the bloodstream, including immunology, oncology, organ transplant biology, reproductive medicine, and stem cell therapies (Hoshimoto et al , 2012; Mathiesen et al , 2012; Danila et al , 2011; Steeg and Theodorescu, 2008; Liu et al , 2009; Wen et al , 2012; Di Marco et al, 2011; He et al, 2011; Egan et al, 2011; Costiniuk et al, 2013; Lopez et al, 2012; Park et al , 2012; Calcaterra et al , 2014). It is common practice amongst researchers to study circulating cells by removing blood samples from the body, which are then analyzed with secondary assays.…”