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.
View: Text | PDF
Article

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

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

×

Figure 4

Options: View larger image (or click on image) Download as PowerPoint
Increased fibronectin content in platelets of Fg–/– and vWF/Fg–/– mice. ...
Increased fibronectin content in platelets of Fg–/– and vWF/Fg–/– mice. For each genotype, platelets were isolated from pooled blood of six mice. Gel-filtered platelets (2 × 107) were analyzed by Western blot. The position of migration of molecular mass standards is shown on the right (in kiloDaltons). Platelet vitronectin (Vn) and thrombospondin-1 (TSP-1) levels were the same in all samples. In contrast, the amount of fibronectin in platelets from either the Fg–/– or vWF/Fg–/– mice was three times greater than from the wild-type mice or vWF–/– mice. The doublet seen with anti–thrombospondin-1 is a consequence of proteolytic cleavage of thrombospondin-1.