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Experimental research
The granulocyte colony-stimulating factor promotes atherosclerosis in high-fat diet rabbits
  1. Zhaohui Hu1,
  2. Hui Gong2,
  3. Ming Yang1,
  4. Yuhong Niu1,
  5. Guoping Zhang2,
  6. Hong Ma1,
  7. Ning Zhou1,
  8. Lei Li2,
  9. Jian Wu2,
  10. Li Lin1,
  11. Aijun Sun1,
  12. Junbo Ge1,
  13. Yunzeng Zou1
  1. 1Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
  2. 2Institutes of Biomedical Science, Fudan University, Shanghai, China

Abstract

Background Granulocyte-colony stimulating factor (G-CSF) has been reported to improve the function of infarcted heart, but its effects on atherosclerosis are unclear.

Methods and Results We examined these and the potential mechanisms in the high-fat diet rabbit model. Six-month-old male New Zealand white rabbits, fed the high-cholesterol (1%) diet or not for 10 weeks, were injected with vehicle or G-CSF (15 μg/kg/day, five days/week for three weeks) subcutaneously daily. G-CSF similarly increased the number of circulating white blood cells (WBC) but not that of platelet both in normal and high-fat diet groups although platelet aggregation function was increased by G-CSF only in normal diet group. G-CSF further increased the plasma levels of total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) at an early phase and atherosclerotic lesions area in the thoracic aorta compared with the vehicle treatment only in high-fat diet group. High-fat diet-induced arterial endothelium damage and collagen hyperplasia were greatly aggravated by G-CSF. G-CSF up-regulated endothelin-1 (ET-1), matrix metalloproteinase (MMP-9) and tissue inhibitor of metalloproteinase-2 (TIMP-2) and down-regulated endothelial nitric oxide synthase (eNOS) expressions in thoracic aorta of high-fat diet groups but did not occur in the normal diet group.

Conclusions The results suggest that G-CSF exacerbates lipid abnormity and endothelium damage in hyperlipidemia rabbits, thereby resulting in the deterioration of atherosclerosis. ET-1/eNOS system and MMP-9/TIMP-2 family may regulate the progression.

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