Role of stromal-derived factor-1alpha 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-1alpha (SDF-1alpha), a key regulator of progenitor cell mobilization, and other cytokines in this process is not clear.


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-1alpha 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-1alpha early after CP/CPB (r=0.56, P<0.01), but not at other times. Protein expression of SDF-1alpha 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-1alpha expression. The numbers of CD34+CXCR4+ progenitor cells positively correlate with the plasma levels of SDF-1alpha post-CP/CPB, suggesting an important role of SDF-1alpha in progenitor cell mobilization.
Mieno
Shigetoshi
S
Division of Cardiothoracic Surgery, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
Ramlawi
Basel
B
Boodhwani
Munir
M
Clements
Richard T
RT
Minamimura
Keisuke
K
Maki
Takashi
T
Xu
Shu-Hua
SH
Bianchi
Cesario
C
Li
Jian
J
Sellke
Frank W
FW
D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood; D006324:Heart Arrest, Induced / Q000009:adverse effects*; D006325:Heart Atria / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D019718:Receptors, CXCR4 / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D018952:Antigens, CD34; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019718:Receptors, CXCR4; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016179:Granulocyte Colony-Stimulating Factor