title: Granulocyte colony stimulating factor in chronic angina to stimulate neovascularisation: a placebo controlled crossover trial.
abstract: BACKGROUND
  Experimental studies demonstrate that granulocyte colony stimulating factor (G-CSF) promotes neovascularisation and confers cardioprotection.
  
  
  OBJECTIVE
  To assess the efficacy of repeated low dose G-CSF plus exercise on myocardial ischaemia in patients with severe chronic ischaemic heart disease.
  
  
  METHODS
  18 patients with Canadian Cardiovascular Society class III-IV angina completed a randomised, double blind, crossover study of dose adjusted G-CSF versus placebo. Exercise was commenced 6 weeks prior and continued for the duration of the study. G-CSF or placebo was administered daily for 5 consecutive days at fortnightly intervals for three cycles, followed by crossover after 6 weeks. Primary outcome was myocardial perfusion by cardiac magnetic resonance imaging (MRI). Secondary outcomes were: Seattle Angina and Utility Based Quality of Life Heart Questionnaire (SAQ/UBQ-H), Exercise Stress Test (EST) and quantification of endothelial progenitor cells (EPC) by flow cytometry and angiogenic cytokines by immunoassay.
  
  
  RESULTS
  Compared with placebo, G-CSF had no effect on myocardial ischaemia by cardiac MRI, EST or SAQ/UBQ-H, despite effective EPC mobilisation (peak fold increase: CD34+ =19, CD34+ CD133+ = 37, CD34+ vascular endothelial growth factor receptor 2 (VEGFR-2)+ = 5, CD34+ CD133+ VEGFR-2+ = 3; all p<0.05 vs. placebo). Plasma levels of stromal cell derived factor 1, angiopoietin 1, interleukin 8 and tumour necrosis factor α decreased after a symptom limited EST while vascular endothelial growth factor and platelet derived growth factor remained unchanged. All cytokines were unchanged following G-CSF. Seven troponin I positive events occurred with G-CSF compared with three with placebo (p=0.289). High sensitivity C reactive protein and N terminal prohormone brain natriuretic peptide increased with G-CSF (both p<0.01 vs. placebo).
  
  
  CONCLUSIONS
  In patients with chronic ischaemic heart disease, G-CSF mobilises EPCs but does not improve myocardial perfusion or angina. G-CSF increases plasma levels of adverse prognostic cardiac biomarkers. Clinical trial registration information Australian New Zealand Clinical Trials Registry: http://www.anzctr.org.au. Unique identifier: ACTRN012607000354482.
authors: Victor Chang Cardiac Research Institute, Lowy Packer Building, 405 Liverpool St, Darlinghurst, NSW 2010, Australia.
authors: Sharon
authors: S
authors: Chih
authors: Peter S
authors: PS
authors: Macdonald
authors: Jane A
authors: JA
authors: McCrohon
authors: David
authors: D
authors: Ma
authors: John
authors: J
authors: Moore
authors: Michael P
authors: MP
authors: Feneley
authors: Matthew
authors: M
authors: Law
authors: Jason C
authors: JC
authors: Kovacic
authors: Robert M
authors: RM
authors: Graham
mesh_terms: D000368:Aged; D000787:Angina Pectoris / Q000188:drug therapy* / Q000473:pathology; D002908:Chronic Disease; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005080:Exercise Test; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D007118:Immunoassay; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D011446:Prospective Studies; D011788:Quality of Life; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D016179:Granulocyte Colony-Stimulating Factor