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Granulocyte Colony-Stimulating Factor Promotes Atherosclerosis in High-Fat Diet Rabbits
Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
Department of Radiology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, China
Department of Cardiology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, China
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 10 October 2012; in revised form: 28 January 2013 / Accepted: 19 February 2013 / Published: 28 February 2013
Abstract: Granulocyte-colony stimulating factor (G-CSF) has been reported to improve the function of infarcted heart, but its effects on atherosclerosis are unclear. Here we examined the effects and the potential mechanisms in the high-fat diet rabbit model. Six-month-old male New Zealand white rabbits, fed a high-cholesterol diet or a normal diet for 10 weeks, were treated with vehicle or G-CSF. G-CSF increased lesion area in the thoracic aorta and the plasma levels of total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) at the early phase in the high-fat diet group. High-fat diet-induced arterial endothelium damage and apoptosis were greatly aggravated by G-CSF treatment. In vivo, G-CSF impaired apoptosis induced by oxidized low density lipoprotein (OX-LDL) but it had little effect on cultured endothelial cells (ECs) with vehicle treatment. Further research revealed that G-CSF promoted the upregulation of endothelin-1 (ET-1) and the downregulation of endothelial nitric oxide synthase (eNOS) of thoracic aortae induced by a high-fat diet. In vitro, the effects of G-CSF on expression of ET-1 and eNOS in cultured ECs were consistent with those in vivo. Our results suggested that G-CSF exacerbates lipid abnormity and endothelium damage in hyperlipidemia rabbits, thereby resulting in the deterioration of atherosclerosis and that the ET-1/eNOS system may regulate the progression.
Keywords: atherosclerosis; endothelial cell; ET-1; G-CSF; apoptosis; hyperlipidemia
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Hu, Z.; Zhang, J.; Guan, A.; Gong, H.; Yang, M.; Zhang, G.; Jia, J.; Ma, H.; Yang, C.; Ge, J.; Zou, Y. Granulocyte Colony-Stimulating Factor Promotes Atherosclerosis in High-Fat Diet Rabbits. Int. J. Mol. Sci. 2013, 14, 4805-4816.
Hu Z, Zhang J, Guan A, Gong H, Yang M, Zhang G, Jia J, Ma H, Yang C, Ge J, Zou Y. Granulocyte Colony-Stimulating Factor Promotes Atherosclerosis in High-Fat Diet Rabbits. International Journal of Molecular Sciences. 2013; 14(3):4805-4816.
Hu, Zhaohui; Zhang, Jie; Guan, Aili; Gong, Hui; Yang, Ming; Zhang, Guoping; Jia, Jianguo; Ma, Hong; Yang, Chunjie; Ge, Junbo; Zou, Yunzeng. 2013. "Granulocyte Colony-Stimulating Factor Promotes Atherosclerosis in High-Fat Diet Rabbits." Int. J. Mol. Sci. 14, no. 3: 4805-4816.