G-CSF induced arteriogenesis in humans: molecular insights into a randomized controlled trial

Curr Vasc Pharmacol. 2013 Jan;11(1):38-46.


Aims: Recent data have demonstrated the feasibility of therapeutic induction of coronary collateral growth (arteriogenesis); however, mechanisms of action of such therapeutic collateral stimulation in humans are unknown. The aim of this study was to evaluate potential mechanisms, especially the involvement of arteriogenesis-relevant genes.

Methods and results: A total of 52 patients were randomized into two groups: subcutaneous G-CSF (10 μg/kg; n=26) or placebo (n=26). Before and after this 2-week treatment, collateral-flow index (CFI) was determined by simultaneous measurement of mean aortic, distal coronary occlusive and central venous pressure. CD34+ endothelial progenitor cells (EPC) and monocytes were quantified before, during and after treatment; gene-expression analysis of monocytes was performed with real-time polymerase chain reaction (RT-PCR). G-CSF lead to a significant increase of EPC and monocytes (4.8 and 2.6 fold, p < 0.05); for both cell types, the extent of increase correlated with CFI increase (r=0.23 and 0.14, p < 0.05). G-CSF also induced a change in gene expression of pro-and anti-arteriogenic genes in monocytes. Among nine assessed genes, three were found to be differentially regulated (IL8, JAK2, and PNPLa4; p < 0.05).

Conclusions: The mechanism of induction of collateral growth by G-CSF is related to an increase of EPC and of peripheral monocytes. It also leads to a change toward a pro-arteriogenic gene expression in peripheral monocytes.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD34 / genetics
  • Antigens, CD34 / metabolism
  • Collateral Circulation / drug effects*
  • Collateral Circulation / physiology*
  • Coronary Artery Disease / drug therapy*
  • Coronary Artery Disease / pathology
  • Coronary Occlusion / drug therapy
  • Coronary Occlusion / genetics
  • Coronary Occlusion / metabolism
  • Coronary Occlusion / physiopathology
  • Double-Blind Method
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Endothelial Cells / physiology
  • Female
  • Gene Expression / drug effects
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Humans
  • Male
  • Middle Aged
  • Monocytes / drug effects
  • Monocytes / metabolism
  • Monocytes / physiology
  • Stem Cells / drug effects
  • Stem Cells / physiology
  • Venous Pressure / drug effects
  • Venous Pressure / genetics
  • Venous Pressure / physiology


  • Antigens, CD34
  • Granulocyte Colony-Stimulating Factor