Effects of granulocyte-colony stimulating factor (G-CSF) on diabetic cardiomyopathy in Otsuka Long-Evans Tokushima Fatty rats

Cardiovascular Diabetology

Original Investigation

Jun-Ho Joe¹  Yi-Sun Song¹  Byung-Im So¹  Ki-Seok Jang²  Young-Hyo Lim³  Cheng-Hu Fang³  Heon-Kil Lim³  Jinho Shin³  Jung-Hyun Kim³  Kyung-Soo Kim⁴ 

[1] Department of Biomedical Sciences, College of Medicine, Hanyang University, Heangdang-Dong 17, Seungdong-ku, Seoul, Korea;Department of Pathology, College of Medicine, Hanyang University, Heangdang-Dong 17, Seungdong-ku, Seoul, Korea;Division of Cardiology, Department of Internal Medicine, College of Medicine, Hanyang University, Heangdang-Dong 17, Seungdong-ku, Seoul, Korea;Division of Cardiology, Department of Internal Medicine, College of Medicine, Hanyang University, Heangdang-Dong 17, Seungdong-ku, Seoul, Korea;Department of Biomedical Sciences, College of Medicine, Hanyang University, Heangdang-Dong 17, Seungdong-ku, Seoul, Korea;

关键词: Diabetes Mellitus;    Cardiomyopathy;    Echocardiography;    Doppler;    Histology;    Fibrosis;   

DOI  :  10.1186/1475-2840-10-92

 received in 2011-08-21, accepted in 2011-10-17,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundDiabetic 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.MethodsTwenty 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.ResultsDiastolic 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.ConclusionsG-CSF can ameliorate cardiac diastolic dysfunction and morphological damage, especially fibrosis of the myocardium, in OLETF rats with diabetic CMP.

【 授权许可】

Unknown   
© Lim et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.