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.
This is an open access article distributed under the
Creative Commons Attribution License which permits unrestricted use, distribution,
and reproduction in any medium, provided the original work is properly cited.
Export to BibTeX
MDPI and ACS Style
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.