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.