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Characterization of Ferric Chloride-Induced Arterial Thrombosis Model of Mice and the Role of Red Blood Cells in Thrombosis Acceleration

 Yeseul Shim  ;  Il Kwon  ;  Youngseon Park  ;  Heow Won Lee  ;  Jayoung Kim  ;  Young Dae Kim  ;  Hyo Suk Nam  ;  Sungha Park  ;  Ji Hoe Heo 
 YONSEI MEDICAL JOURNAL, Vol.62(11) : 1032-1041, 2021-11 
Journal Title
Issue Date
Acceleration ; Animals ; Chlorides ; Erythrocytes ; Ferric Compounds ; Mice ; Mice, Inbred C57BL ; Thrombosis* / chemically induced
Thrombosis ; experimental animal models ; platelet ; red blood cells
Purpose: The ferric chloride (FeCl3)-induced thrombosis model is widely used for thrombosis research. However, it lacks standardization with uncertainty in the exact mechanism of thrombosis. This study aimed to characterize thrombus formation in a mouse model.

Materials and methods: We investigated thrombus formation and stability using various FeCl3 concentrations (10%, 20%, 30%, 40%, and 50%, w/v) in carotid arteries of the Institute of Cancer Research (ICR) and C57BL/6N mice using the FeCl3-induced thrombosis model. We also investigated thrombus histopathology using immunohistochemistry and electron microscopy.

Results: Higher FeCl3 concentrations induced dose-dependent, faster, larger, and more stable thrombus formation in both strains of mice. However, the ICR mice showed better dose-responses in thrombus formation and stability compared to the C57BL/6N mice. Thrombi were fibrin- and platelet-rich without significant changes across FeCl3 concentrations. However, the content of red blood cells (RBCs) increased with increasing FeCl3 concentrations (p for trend <0.001) and inversely correlated with time to occlusion (r=-0.65, p<0.001). While platelets and fibrin were evenly distributed over the thrombus, RBCs were predominantly located near the FeCl3 treatment area. Transmission electron microscopy showed that RBCs attached to and were surrounded by aggregates of degranulated platelets, suggesting their potential role in platelet activation.

Conclusion: Faster and larger thrombus formation is induced in a dose-dependent manner by a wide range of FeCl3 concentrations, but the stable thrombus formation requires higher FeCl3 concentrations. Mouse strain affects thrombus formation and stability. RBCs and their interaction with platelets play a key role in the acceleration of FeCl3-induced thrombosis.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
Kwon, Il(권일) ORCID logo https://orcid.org/0000-0001-9449-5646
Kim, Young Dae(김영대) ORCID logo https://orcid.org/0000-0001-5750-2616
Nam, Hyo Suk(남효석) ORCID logo https://orcid.org/0000-0002-4415-3995
Park, Sung Ha(박성하) ORCID logo https://orcid.org/0000-0001-5362-478X
Lee, Heow Won(이효원)
Heo, Ji Hoe(허지회) ORCID logo https://orcid.org/0000-0001-9898-3321
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