title: Effects of granulocyte-colony stimulating factor (G-CSF) on diabetic cardiomyopathy in Otsuka Long-Evans Tokushima fatty rats.
abstract: BACKGROUND
  Diabetic cardiomyopathy (CMP) is a common and disabling disease in diabetic patients, however no effective treatments have been developed. Although granulocyte-colony stimulating factor (G-CSF) improves heart function in myocardial infarction, its effect on non-ischemic CMP such as diabetic CMP is unknown. In the present study, we investigated the effects of G-CSF on diabetic CMP in a rat model of type II diabetes.
  
  
  METHODS
  Twenty 7-week-old male Otsuka Long-Evans Tokushima Fatty (OLETF: a rat model of diabetes) rats and 10 male Long-Evans Tokushima Otsuka (LETO: normal controls) rats were used. All of the LETO and 8 OLETF rats were fed on tap water while the rest were fed on sucrose-containing water. After 10 weeks, saline or recombinant human G-CSF (100 μg/kg/day) was injected intraperitoneally for 5 days. Blood levels of glucose, total cholesterol and triglyceride, and Doppler echocardiograms for diastolic dysfunction were obtained just before and 4 weeks after the saline or G-CSF treatment. Light microscopy, electron microscopy (EM) and immunohistochemistry for transforming growth factor-β were employed to examine myocardial histology 4 weeks after the saline or G-CSF treatment.
  
  
  RESULTS
  Diastolic dysfunction developed at 17 weeks (before the saline or G-CSF treatment) in the OLETF rats whether or not they were fed sucrose water, but were more severe in those fed sucrose water. Four weeks after saline or G-CSF treatment, diastolic function had recovered in the G-CSF-treated group regardless of sucrose water feeding, and perivascular and/or interstitial fibrosis in the G-CSF-treated group had decreased significantly. TGF-β immunoreactivity in the interstitial and perivascular tissue was also reduced in the G-CSF-treated group, and EM studies revealed less severe disruption of myofilaments and mitochondrial cristae, and decreased collagen deposition.
  
  
  CONCLUSIONS
  G-CSF can ameliorate cardiac diastolic dysfunction and morphological damage, especially fibrosis of the myocardium, in OLETF rats with diabetic CMP.
authors: Division of Cardiology, Department of Internal Medicine, College of Medicine, Hanyang University, Seungdong-ku, Seoul, Korea.
authors: Young-Hyo
authors: YH
authors: Lim
authors: Jun-Ho
authors: JH
authors: Joe
authors: Ki-Seok
authors: KS
authors: Jang
authors: Yi-Sun
authors: YS
authors: Song
authors: Byung-Im
authors: BI
authors: So
authors: Cheng-Hu
authors: CH
authors: Fang
authors: Jinho
authors: J
authors: Shin
authors: Jung-Hyun
authors: JH
authors: Kim
authors: Heon-Kil
authors: HK
authors: Lim
authors: Kyung-Soo
authors: KS
authors: Kim
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D058065:Diabetic Cardiomyopathies / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004719:Endomyocardial Fibrosis / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008297:Male; D051381:Rats; D020334:Rats, Inbred OLETF; D020318:Rats, Long-Evans
chemical_list: D016179:Granulocyte Colony-Stimulating Factor