High-Dose Granulocyte-Colony Stimulating Factor Promotes Neointimal Hyperplasia in the Early Phase and Inhibits Neointimal Hyperplasia in the Late Phase After Vascular Injury

Makoto Shoji; Yoshitaka Iso; Taro Kusuyama; Yasutoshi Omori; Teruko Soda; Fumiyoshi Tsunoda; Takatoshi Sato; Shinji Koba; Eiichi Geshi; Youichi Kobayashi; Takashi Katagiri; Hiroshi Suzuki

doi:10.1253/circj.CJ-07-1037

Experimental Investigation

High-Dose Granulocyte-Colony Stimulating Factor Promotes Neointimal Hyperplasia in the Early Phase and Inhibits Neointimal Hyperplasia in the Late Phase After Vascular Injury

Makoto Shoji, Yoshitaka Iso, Taro Kusuyama, Yasutoshi Omori, Teruko Soda, Fumiyoshi Tsunoda, Takatoshi Sato, Shinji Koba, Eiichi Geshi, Youichi Kobayashi, Takashi Katagiri, Hiroshi Suzuki

Author information

Makoto Shoji
Third Department of Internal Medicine, Showa University School of Medicine
Yoshitaka Iso
Third Department of Internal Medicine, Showa University School of Medicine
Taro Kusuyama
Third Department of Internal Medicine, Showa University School of Medicine
Yasutoshi Omori
Third Department of Internal Medicine, Showa University School of Medicine
Teruko Soda
Third Department of Internal Medicine, Showa University School of Medicine
Fumiyoshi Tsunoda
Third Department of Internal Medicine, Showa University School of Medicine
Takatoshi Sato
Third Department of Internal Medicine, Showa University School of Medicine
Shinji Koba
Third Department of Internal Medicine, Showa University School of Medicine
Eiichi Geshi
Third Department of Internal Medicine, Showa University School of Medicine
Youichi Kobayashi
Third Department of Internal Medicine, Showa University School of Medicine
Takashi Katagiri
Third Department of Internal Medicine, Showa University School of Medicine
Hiroshi Suzuki
Division of Cardiology, Department of Internal Medicine, Showa University Fujigaoka Hospital

Keywords: Bone-marrow-derived cell, CD34, G-CSF, Neointima, Re-endothelialization

JOURNAL FREE ACCESS

2008 Volume 72 Issue 11 Pages 1885-1893

DOI https://doi.org/10.1253/circj.CJ-07-1037

View "Advance Publication" version (October 7, 2008).

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Abstract

Background Granulocyte-colony stimulating factor (G-CSF) affects injured arteries through early endothelialization. Some reports, however, have cautioned that the restenosis rate may increase after G-CSF injection. In the present study, high-dose G-CSF was administered to mice with vascular injury to clarify its effect. Methods and Results Mice were received daily subcutaneous injections of saline or a high dose (300 μg/kg) of G-CSF for 5 days after vascular injury. In the FACS analysis, CD34-/Sca-1-positive progenitor cells were more abundant in the G-CSF group (p<0.05). Neointimal hyperplasia was more evident in the G-CSF group at 1 week (p<0.05), whereas at 4 weeks it was more evident in the control group (p<0.01). TUNEL-positive cells in the arterial wall were more numerous in the G-CSF group at day 1 (p<0.01). CD34-positive cells were observed in the G-CSF group at 1 week. Re-endothelialization appeared earlier in the G-CSF group (at 4 weeks; p<0.01). An increased number of 1A4-positive smooth muscle cells were found in bone marrow cell culture treated with G-CSF. Conclusion High-dose G-CSF induced neointimal proliferation through excessive inflammation and bone marrow cell mobilization in the early phase. In the late phase, however, it induced early re-endothelialization and thereby inhibited neointimal hyperplasia. (Circ J 2008; 72: 1885 - 1893)

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