title: G-CSF induced arteriogenesis in humans: molecular insights into a randomized controlled trial.
abstract: OBJECTIVE
  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.
  
  
  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.
authors: The Heart Hospital, University College London Hospitals, London, UK.
authors: Pascal
authors: P
authors: Meier
authors: Steffen
authors: S
authors: Gloekler
authors: Berna
authors: B
authors: Oezdemir
authors: Andreas
authors: A
authors: Indermuehle
authors: Tobias
authors: T
authors: Traupe
authors: Rolf
authors: R
authors: Vogel
authors: Stefano
authors: S
authors: de Marchi
authors: Christian
authors: C
authors: Seiler
mesh_terms: D018952:Antigens, CD34 / Q000235:genetics / Q000378:metabolism; D003097:Collateral Circulation / Q000187:drug effects* / Q000502:physiology*; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000473:pathology; D054059:Coronary Occlusion / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D004311:Double-Blind Method; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology; D014690:Venous Pressure / Q000187:drug effects / Q000235:genetics / Q000502:physiology
chemical_list: D018952:Antigens, CD34; D016179:Granulocyte Colony-Stimulating Factor