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Persistence of platelet thrombus formation in arterioles of mice lacking both von Willebrand factor and fibrinogen
Heyu Ni, … , Richard O. Hynes, Denisa D. Wagner
Heyu Ni, … , Richard O. Hynes, Denisa D. Wagner
Published August 1, 2000
Citation Information: J Clin Invest. 2000;106(3):385-392. https://doi.org/10.1172/JCI9896.
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Article Article has an altmetric score of 6

Persistence of platelet thrombus formation in arterioles of mice lacking both von Willebrand factor and fibrinogen

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Abstract

We used intravital microscopy to observe the formation of platelet plugs in ferric chloride–injured arterioles of live mice. With this model, we evaluated thrombus growth in mice lacking von Willebrand factor (vWF) and fibrinogen (Fg), the two key ligands known to mediate platelet adhesion and aggregation. In vWF–/– mice, despite the presence of arterial shear, delayed platelet adhesion occurred and stable thrombi formed. In many mice, a persisting high-shear channel never occluded. Abundant thrombi formed in Fg–/– mice, but they detached from the subendothelium, which ultimately caused downstream occlusion in all cases. Surprisingly, mice deficient in both vWF and Fg successfully formed thrombi with properties characteristic of both mutations, leading to vessel occlusion in the majority of vessels. Platelets of these doubly deficient mice specifically accumulated fibronectin in their α-granules, suggesting that fibronectin could be the ligand supporting the platelet aggregation.

Authors

Heyu Ni, Cécile V. Denis, Sangeetha Subbarao, Jay L. Degen, Thomas N. Sato, Richard O. Hynes, Denisa D. Wagner

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Figure 3

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Quantitative analysis of thrombi formation in wild-type and mutant arter...
Quantitative analysis of thrombi formation in wild-type and mutant arterioles. (a) Frequent occurrence of narrow flow channels in thrombi of arterioles in vWF–/– mice. Small channels within thrombi lasting more than 5 minutes were recorded and their frequency established for each genotype. Thrombi in nine out of 10 vessels in vWF–/– mice formed these channels in the late stage, which was a frequency significantly higher than in wild-type mice (1/12) (χ2 = 14.66, P < 0.005) or in other genotypes of mice. (b) The effects of vWF or Fg deficiency on vessel occlusion time. The time before blood flow completely stopped in each vessel was determined. If blood flow did not cease during the 40-minute observation period, 40 minutes was used as the occlusion time. Surprisingly, the time needed to stop blood flow in Fg–/– arterioles was similar to wild-type. The occlusion time in vWF-knockout mice was longer than that of double-knockout mice (P < 0.01), where embolization led to a more rapid thrombus accumulation, and both were prolonged in comparison with wild-type. The P values shown in this figure were determined by comparison with wild-type arterioles. (c) The roles of vWF or Fg in thrombus embolization. The number of large emboli (diameter > 30 μm) generated in the period before vessel occlusion was determined. Although this period was short in Fg–/– mice, the number of emboli formed in these mice was the highest. However, no statistically significant difference was found between Fg–/– mice and double knockouts (P = 0.07). The P values shown in this figure were determined by comparison with wild-type arterioles.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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Referenced in 4 patents
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