Role of Stromal-Derived Factor-1 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 (SDF-1 ), 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 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 early after CP/CPB (r 0.56, P 0.01), but not at other times. Protein expression of SDF-1 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 expression. The numbers of CD34 CXCR4 progenitor cells positively correlate with the plasma levels of SDF-1 post-CP/CPB, suggesting an important role of SDF-1 in progenitor cell mobilization. (Circulation. 2006;114[suppl I]:I-186–I-192.)