Role of Stromal-Derived Factor-1α in the Induction of Circulating CD34+CXCR4+ Progenitor Cells After Cardiac Surgery

Abstract

Background— Cardioplegia and cardiopulmonary bypass (CP/CPB) leads to an increase in circulating progenitor cells. The role of stromal-derived factor-1α (SDF-1α), a key regulator of progenitor cell mobilization, and other cytokines in this process is not clear. Methods and Results— Peripheral blood (n=24), atrial and skeletal tissue (n=6) samples were taken from patients undergoing CP/CPB before (pre-CP/CPB), 4 hours (post-CP/CPB), and 4 days (POD4) after CP/CPB. The number of circulating CD34+CXCR4+ cells increased post-CP/CPB (442±53 versus 286±27; P =0.04 versus pre-CP/CPB), but not at POD4 (382±50; P =0.28 versus pre-CP/CPB). Plasma levels of SDF-1α increased post-CP/CPB as compared with pre-CP/CPB (3325±325 versus 2911±165 pg/mL; P =0.046) but returned to baseline at POD4 (2838±224 pg/mL; P =0.90). Plasma levels of vascular endothelial growth factor were similar post-CP/CPB ( P =0.90 versus pre-CP/CPB) but increased at POD4 (220±40 pg/mL versus 134±26 pg/mL; P =0.04 versus pre-CP/CPB). Serum levels of granulocyte-colony stimulating factor (G-CSF) increased early after CP/CPB as compared with pre-CP/CPB (265.0±41.7 versus 11.1±1.1 pg/mL; P <0.001) and returned to baseline at POD4 ( P =0.84 versus pre-CP/CPB). The circulating CD34+CXCR4+ cells were positively correlated with plasma levels of SDF-1α early after CP/CPB ( r =0.56, P <0.01), but not at other times. Protein expression of SDF-1α was elevated in the atrial myocardium after CP/CPB (9.4-fold; P =0.03). Conclusions— Exposure to CP/CPB leads to an increase in circulating CD34+CXCR4+ progenitor cells, which is associated with increased myocardial SDF-1α expression. The numbers of CD34+CXCR4+ progenitor cells positively correlate with the plasma levels of SDF-1α post-CP/CPB, suggesting an important role of SDF-1α in progenitor cell mobilization.