Role of stromal-derived factor-1α in the induction of circulating CD34+ CXCR4+ progenitor cells after cardiac surgery

Background-Cardioplegia and cardiopulmonary bypass (CP/CPB) leads to an increase in circulating progenitor cells. The role of stromal-derived factor-1 alpha (SDF-1 alpha), 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-1 alpha 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-1 alpha early after CP/CPB (r = 0.56, P < 0.01), but not at other times. Protein expression of SDF-1 alpha 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-1 alpha expression. The numbers of CD34+CXCR4+ progenitor cells positively correlate with the plasma levels of SDF-1 alpha post-CP/CPB, suggesting an important role of SDF-1 alpha in progenitor cell mobilization.