Potent cholesterol-lowering effect by human granulocyte-macrophage colony- stimulating factor in rabbits: Possible implications of enhancement of macrophage functions and an increase in mRNA for VLDL receptor

T. Ishibashi, K. Yokoyama, J. Shindo, Y. Hamazaki, Y. Endo, T. Sato, S. Takahashi, Y. Kawarabayasi, M. Shiomi, T. Yamamoto, Y. Maruyama

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Abstract

The mechanism by which granulocyte-macrophage colony-stimulating factor (GM-CSF) lowers plasma cholesterol levels is not well understood. We tested recombinant human GM-CSF (rhGM-CSF) on plasma cholesterol and triglycerides in rabbits and attempted to determine the mechanisms of the cholesterol- lowering effect. rhGM-CSF (20 μg · kg-1 · d-1) was administered to normal and cholesterol-fed rabbits for 2 weeks and to Watanabe heritable hyperlipidemic (WHHL) rabbits for 1 week. The administration of rhGM-CSF markedly lowered cholesterol and triglycerides, an effect that persisted in normal and cholesterol-fed rabbits even after termination of treatment. The cholesterol-lowering effect of rhGM-CSF was also observed in WHHL rabbits. rhGM-CSF was capable of stimulating granulocyte-macrophage colony formation in vitro in rabbits with an effect comparable to that in humans. Northern blot analysis with rabbit very-low-density-lipoprotein (VLDL) receptor cDNA revealed that rhGM-CSF increased the levels of VLDL receptor mRNA in muscle of rabbits after only 1.5 hours of treatment compared with control (2.6- fold), with the 1.5-fold increase following a 5-day administration. No changes in the levels of LDL receptor mRNA in liver, spleen, and bone marrow were observed in the treated rabbits. These findings suggest that the cholesterol-lowering effect of rhGM-CSF may be mediated by enhancement of macrophage functions in lipid metabolism and the increase in mRNA for VLDL receptor in rabbits.

Original languageEnglish
Pages (from-to)1534-1541
Number of pages8
JournalArteriosclerosis and Thrombosis
Volume14
Issue number10
Publication statusPublished - 1994 Jan 1

Keywords

  • VLDL receptor
  • cholesterol
  • granulocyte-macrophage colony-stimulating factor
  • macrophages
  • triglycerides

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Ishibashi, T., Yokoyama, K., Shindo, J., Hamazaki, Y., Endo, Y., Sato, T., Takahashi, S., Kawarabayasi, Y., Shiomi, M., Yamamoto, T., & Maruyama, Y. (1994). Potent cholesterol-lowering effect by human granulocyte-macrophage colony- stimulating factor in rabbits: Possible implications of enhancement of macrophage functions and an increase in mRNA for VLDL receptor. Arteriosclerosis and Thrombosis, 14(10), 1534-1541.