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

Circulation. 2006 Jul 4;114(1 Suppl):I186-92. doi: 10.1161/circulationaha.105.001610.

Abstract

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.

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-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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Antigens, CD34 / analysis
  • Cardiac Surgical Procedures*
  • Cardiopulmonary Bypass / adverse effects*
  • Chemokine CXCL12
  • Chemokines, CXC / biosynthesis
  • Chemokines, CXC / blood
  • Chemokines, CXC / genetics
  • Chemokines, CXC / physiology*
  • Female
  • Gene Expression Regulation
  • Granulocyte Colony-Stimulating Factor / blood
  • Heart Arrest, Induced / adverse effects*
  • Heart Atria / metabolism
  • Hematopoietic Stem Cells / physiology*
  • Humans
  • Inflammation / blood
  • Inflammation / etiology
  • Inflammation / physiopathology*
  • Male
  • Receptors, CXCR4 / analysis
  • Vascular Endothelial Growth Factor A / blood

Substances

  • Antigens, CD34
  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines, CXC
  • Receptors, CXCR4
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Granulocyte Colony-Stimulating Factor