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Updated: Jun 29, 2026
Quantitative Analysis and Characterization of Atherosclerotic Lesions in the Murine Aortic Sinus
Published on: December 7, 2013
Granulocyte colony-stimulating factor has no adverse effects on atherosclerotic lesions in high cholesterol-fed
Hirotake Takai1, Akio Miyoshi, Masaki Yamazaki
1Department of Safety Assessment, Fuji Gotemba Research Laboratory, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan. takaihrt@chugai-pharm.co.jp
Insights
Granulocyte colony-stimulating factor (G-CSF) did not worsen atherosclerosis in swine models. This study found G-CSF safe for treating coronary artery disease patients, despite increasing white blood cell counts.
Area of Science:
- Cardiovascular Science
- Hematology
- Pharmacology
Background:
- Granulocyte colony-stimulating factor (G-CSF) is used for stem cell mobilization and investigated for cardiac repair in coronary artery disease.
- Atherosclerosis progression is a key concern for G-CSF safety in these patients.
- The safety of G-CSF administration in patients with coronary artery disease requires further investigation.
Purpose of the Study:
- To evaluate the safety and effects of G-CSF on existing atherosclerotic lesions in an animal model.
- To determine if G-CSF exacerbates or modifies atherosclerosis progression.
- To assess general toxicological effects of G-CSF in the context of atherosclerosis.
Main Methods:
- An atherosclerosis animal model was created in miniature swine using a high-cholesterol diet.
- G-CSF was administered via daily subcutaneous injections for 10 days.
- Pathological evaluation of 20 main arteries and general toxicological assessments were performed.
Main Results:
- G-CSF treatment led to expected increases in white blood cell (WBC) counts.
- No significant changes in the histopathology, incidence, severity, or distribution of atherosclerotic lesions were observed.
- No neutrophil infiltration into atherosclerotic lesions was detected, and no adverse general toxicological effects were noted.
Conclusions:
- G-CSF administration did not exacerbate or modify atherosclerotic lesions in this swine model.
- G-CSF appears safe for use in patients with coronary artery disease, even with induced increases in WBC counts.
- These findings support the potential therapeutic use of G-CSF in cardiovascular conditions without negatively impacting atherosclerosis.
Abstract:
Granulocyte colony-stimulating factor (G-CSF) is widely used to mobilize peripheral blood stem cells, and expected to restore cardiac function for patients with coronary artery diseases as a consequence of progression of atherosclerosis. Safety issues related to the administration of G-CSF to these patients, however, are still under study. The animal model for atherosclerosis was produced by feeding miniature swine a high-cholesterol diet for 3 months. G-CSF (5 or 10 microg/kg/day) was given to the animal model by daily subcutaneous injections for 10 days and 20 main arteries were evaluated pathologically. In addition, the general toxicological effects were studied on clinical signs, body weight, hematology, blood chemistry and pathology. In the G-CSF-treated groups, a variety of changes related to the major pharmacological activity of G-CSF including an increase in white blood cell (WBC) counts were observed. In many arteries, atherosclerotic lesions similar to Type I-V of the proposed classification by the American Heart Association were observed. No effects of the G-CSF treatment were seen on the histopathological findings, incidence, severity or distribution of atherosclerotic lesions. In addition, no infiltration of neutrophils to the lesions was observed. These findings suggest that the administration of G-CSF causes neither exacerbation or modification of atherosclerotic lesions nor adverse changes despite that a sufficient increase in WBC counts could be achieved in the peripheral blood.
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