title: Granulocyte colony-stimulating factor reduces cardiomyocyte apoptosis and improves cardiac function in adriamycin-induced cardiomyopathy in rats.
abstract: BACKGROUND
  Cardiomyocyte apoptosis reportedly participates in the occurrence and progression of dilated cardiomyopathy (DCM). Recent studies have shown that granulocyte colony-stimulating factor (G-CSF) enhances bone marrow cells migration to the damaged heart in the DCM model and improves the ultrastructure of the cardiomyocyte in adriamycin (ADR) induced DCM. However, its influence on cardiac pump function and cardiomyocyte apoptosis has not been studied.
  
  
  METHODS
  Wistar Rats were randomly grouped into control, ADR, ADR+PBS, ADR+G-CSF group (n = 10). ADR (2.5 mg/kg, 6 times for 2 weeks) was administered intraperitoneally in all rats except the control group. After 2 weeks, the rats in ADR+G-CSF group were injected with G-CSF (50 microg/kg/day for 8 days) subcutaneously. Cardiac function was evaluated by echocardiogram and cardiac catheterization after 4 weeks. Cardiomyocytes apoptosis and apoptosis-related protein Fas were detected by in situ terminal deoxynucleotidyl transferase assay (TUNEL method) and Western blot, respectively.
  
  
  RESULTS
  The ADR and ADR+PBS groups showed significant deteriorations of left ventricular functions and high cardiomyocyte apoptosis index, as well as high Fas expressions. Meanwhile, the ADR+G-CSF group showed significant improvement in LV function, inhibition of cardiomyocyte apoptosis compared with the ADR and ADR+Phosphate-Buffered Saline PBS group. The Fas protein expression was remarkably attenuated as well.
  
  
  CONCLUSIONS
  Our results suggest that administration of G-CSF inhibited cardiomyocyte apoptosis and Fas protein expression and contributes to improving cardiac pump function in vivo in ADR induced DCM rat model.
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 30020, China.
authors.forename: Xu Wei
authors.initials: XW
authors.lastname: Hou
authors.forename: Ja
authors.initials: J
authors.lastname: Son
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Yong Xin
authors.initials: YX
authors.lastname: Ru
authors.forename: Qing
authors.initials: Q
authors.lastname: Lian
authors.forename: Wuliya
authors.initials: W
authors.lastname: Majiti
authors.forename: A
authors.initials: A
authors.lastname: Amazouzi
authors.forename: Yu Ling
authors.initials: YL
authors.lastname: Zhou
authors.forename: Pei Xian
authors.initials: PX
authors.lastname: Wang
authors.forename: Zhong Chao
authors.initials: ZC
authors.lastname: Han
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002311:Cardiomyopathy, Dilated / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage / Q000633:toxicity*; D004452:Echocardiography; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D020287:In Situ Nick-End Labeling; D007279:Injections, Subcutaneous; D008297:Male; D008854:Microscopy, Electron; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D017725:Ventricular Pressure / Q000187:drug effects; D019014:fas Receptor
chemical_list: D000903:Antibiotics, Antineoplastic; C491898:Fas protein, rat; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor; D016179:Granulocyte Colony-Stimulating Factor; D004317:Doxorubicin