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Updated: Jun 2, 2026
Ferric Chloride-induced Murine Thrombosis Models
Published on: September 5, 2016
Granulocyte-CSF induced inflammation-associated cardiac thrombosis in iron loading mouse heart and can be attenuated
Wei S Lian1, Heng Lin, Winston Tk Cheng
1Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Insights
Granulocyte colony-stimulating factor (G-CSF) can cause cardiac thrombosis by promoting inflammation. Statin therapy effectively prevents this thrombosis by reducing inflammation and leukocytosis, offering a potential therapeutic strategy.
Area of Science:
- Cardiovascular Research
- Hematology
- Pharmacology
Background:
- Granulocyte colony-stimulating factor (G-CSF) shows therapeutic potential in acute myocardial infarction but carries risks of re-stenosis and condition worsening.
- A novel disease model is presented to investigate G-CSF-induced cardiac thrombosis and its underlying mechanisms.
Purpose of the Study:
- To establish a mouse model for studying G-CSF-induced cardiac thrombosis.
- To elucidate the mechanism by which G-CSF contributes to cardiac thrombosis.
- To evaluate potential therapeutic interventions for G-CSF-induced cardiac thrombosis.
Main Methods:
- Iron loading was used to induce chronic cardiac dysfunction in mice.
- Granulocyte colony-stimulating factor (G-CSF) was administered to mice to induce thrombosis.
- Simvastatin and tirofiban were used to test therapeutic interventions.
Main Results:
- Iron and G-CSF treated mice (I+G) exhibited thrombi formation in the left ventricle and impaired cardiac function.
- Histological analysis of I+G mice revealed endothelial fibrosis, macrophage infiltration, and tissue factor expression.
- Simvastatin treatment attenuated cardiac apoptosis, iron deposition, and abrogated thrombosis by reducing inflammation and leukocytosis, possibly via pAKT activation.
- Tirofiban failed to suppress thrombosis in I+G mice.
Conclusions:
- G-CSF induces cardiac thrombosis via an inflammation-thrombosis interaction.
- Statin therapy can attenuate G-CSF-induced cardiac thrombosis.
- This study provides a mechanistic understanding and potential therapeutic approach for G-CSF-induced cardiac thrombosis.
Background:
Granulocyte colony-stimulating factor (G-CSF), a hematopoietic cytokine, was recently used to treat patients of acute myocardial infarction with beneficial effect. However, controversy exists as some patients developed re-stenosis and worsened condition post G-CSF delivery. This study presents a new disease model to study G-CSF induced cardiac thrombosis and delineate its possible mechanism. We used iron loading to mimic condition of chronic cardiac dysfunction and apply G-CSF to mice to test our hypothesis.
Methods And Results:
Eleven out of fifteen iron and G-CSF treated mice (I+G) showed thrombi formation in the left ventricular chamber with impaired cardiac function. Histological analysis revealed endothelial fibrosis, increased macrophage infiltration and tissue factor expression in the I+G mice hearts. Simvastatin treatment to I+G mice attenuated their cardiac apoptosis, iron deposition, and abrogated thrombus formation by attenuating systemic inflammation and leukocytosis, which was likely due to the activation of pAKT activation. However, thrombosis in I+G mice could not be suppressed by platelet receptor inhibitor, tirofiban.
Conclusions:
Our disease model demonstrated that G-CSF induces cardiac thrombosis through an inflammation-thrombosis interaction and this can be attenuated via statin therapy. Present study provides a mechanism and potential therapy for G-CSF induced cardiac thrombosis.
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