- 作者: Wei S Lian; Heng Lin; Winston T.K. Cheng; Tateki Kikuchi; Ching F Cheng
- 作者服務機構: Department of Medical Research, Tzu Chi General Hospital and Department of Pediatrics, Tzu Chi University, Taiwan, R.O.C.
- 中文摘要: --
- 英文摘要:
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. - 中文關鍵字: --
- 英文關鍵字: --