Early Outgrowth Pro-Angiogenic Cell Number and Function Do Not Correlate with Left Ventricular Structure and Function in Conventional Hemodialysis Patients: A Cross-Sectional Study

Abstract

Background: Left ventricular hypertrophy (LVH) is commonly found in chronic dialysis (CD) recipients, and is associated with impaired microvascular cardiac perfusion and heart failure. In response to LVH and cardiac ischemia, early outgrowth pro-angiogenic cellS(EPCs) mobilize from the bone marrow to facilitate angiogenesis and endothelial repair. In the general population, EPC number and function correlate inversely with cardiovascular risk. In end-stage renal disease (ESRD), EPC number and function are generally reduced. Objectives: To test whether left ventricular abnormalities retain their potent ability to promote EPC reparative responses in the setting of ESRD. Design: Cross-sectional study. Setting: St. Michael's Hospital, Toronto, Ontario, Canada. Patients: 47 prevalent chronic dialysis recipients. Measurements: (1) circulating CD34 + and CD133 + EPC number, (2) cultured EPC migratory ability, in vitro differentiation potential, and apoptosis rate, and (3) cardiac magnetic resonance-measured LV mass, volume and ejection fraction. Methods: Bivariate correlation analysis was performed with Spearman's rho test. Results: Of the 47 patients (mean age: 54 ± 13 years), the mean delivered urea reduction was 74 ± 10 %. Mean LV mass was 123 ± 38 g. Circulating CD34 + and CD133 + EPCs represented 0.14 % (IQR: 0.05 – 0.29 %) and 0.05 % (IQR: 0.01 – 0.10 %) of peripheral blood mononuclear cells. There were no significant correlations between any EPC parameter and measures of LV mass or ejection fraction. Limitations: Lack of a non-ESRD control population, and the inability to measure all parameters of EPC function due to limitations in blood sampling. Our inability to measure cardiac VEGF expression prevented an assessment of changes in cardiac EPC mobilization signals. Conclusions: These data suggest that in ESRD, the reparative EPC response to cardiac hypertrophy may be blunted. Further investigation of the effects of uremia on EPC physiology and its relationship to cardiac injury are required.