title: Granulocyte colony-stimulating factor promotes atherosclerosis in high-fat diet rabbits.
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.
authors: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China. zou.yunzeng@zs-hospital.sh.cn.
authors: Zhaohui
authors: Z
authors: Hu
authors: Jie
authors: J
authors: Zhang
authors: Aili
authors: A
authors: Guan
authors: Hui
authors: H
authors: Gong
authors: Ming
authors: M
authors: Yang
authors: Guoping
authors: G
authors: Zhang
authors: Jianguo
authors: J
authors: Jia
authors: Hong
authors: H
authors: Ma
authors: Chunjie
authors: C
authors: Yang
authors: Junbo
authors: J
authors: Ge
authors: Yunzeng
authors: Y
authors: Zou