title: Stimulation of coronary collateral growth by granulocyte stimulating factor: role of reactive oxygen species.
abstract: OBJECTIVE
  The purpose of this study was to determine whether G-CSF promotes coronary collateral growth (CCG) and decipher the mechanism for this stimulation.
  
  
  RESULTS
  In a rat model of repetitive episodic myocardial ischemia (RI, 40 seconds LAD occlusion every 20 minutes for 2 hours and 20 minutes, 3 times/d for 5 days) CCG was deduced from collateral-dependent flow (flow to LAD region during occlusion). After RI, G-CSF (100 microg/kg/d) increased CCG (P<0.01) (0.47+/-0.15) versus vehicle (0.14+/-0.06). Surprisingly, G-CSF treatment without RI increased CCG (0.57+/-0.18) equal to G-CSF+RI. We evaluated ROS by dihydroethidine (DHE) fluorescence (LV injection, 60 microg/kg, during two episodes of ischemia). DHE fluorescence was double in G-CSF+RI versus vehicle+RI (P<0.01), and even higher in G-CSF without RI (P<0.01). Interestingly, the DHE signal did not colocalize with myeloperoxidase (immunostaining, neutrophil marker) but appeared in cardiac myocytes. The study of isolated cardiac myocytes revealed the cytokine stimulates ROS which elicit production of angiogenic factors. Apocynin inhibited G-CSF effects both in vivo and in vitro.
  
  
  CONCLUSIONS
  G-CSF stimulates ROS production directly in cardiomyocytes, which plays a pivotal role in triggering adaptations of the heart to ischemia including growth of the coronary collaterals.
authors: Centre for Cardiovascular Research, Charité Medical University, Berlin, Germany.
authors: Ana Catarina R
authors: AC
authors: Carrão
authors: William M
authors: WM
authors: Chilian
authors: June
authors: J
authors: Yun
authors: Christopher
authors: C
authors: Kolz
authors: Petra
authors: P
authors: Rocic
authors: Kerstin
authors: K
authors: Lehmann
authors: Jeroen P H M
authors: JP
authors: van den Wijngaard
authors: Pepijn
authors: P
authors: van Horssen
authors: Jos A E
authors: JA
authors: Spaan
authors: Vahagn
authors: V
authors: Ohanyan
authors: Yuh Fen
authors: YF
authors: Pung
authors: Ivo
authors: I
authors: Buschmann
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D003097:Collateral Circulation / Q000187:drug effects / Q000502:physiology*; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004452:Echocardiography; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism* / Q000494:pharmacology; D006334:Heart Function Tests; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012016:Reference Values
chemical_list: D017382:Reactive Oxygen Species; D016179:Granulocyte Colony-Stimulating Factor