Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
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 Article has an altmetric score of 6

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

  • Text
  • PDF
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 2

Options: View larger image (or click on image) Download as PowerPoint
Characteristics of thrombus growth differ with mouse genotype. Times aft...
Characteristics of thrombus growth differ with mouse genotype. Times after FeCl3-induced injury are indicated (min). In wild-type mice (WT), numerous adherent fluorescently labeled platelets can be seen 4 minutes after FeCl3 treatment. Thrombi usually grow fast and cause vessels to occlude at the site of injury (15 minutes). In vWF–/– mice, very few platelet–vessel wall interactions were seen at the early time points, but thrombus formation occurred (13 minutes). Thrombi usually stopped growing at the later times, leaving a small channel open (arrowheads, 29 minutes) with high shear flow. The dark thrombus at this time point indicates that few new platelets were recruited, and platelet fluorescence was bleached after a long exposure to UV light. In Fg–/– mice, early platelet depositions were similar to wild-type mice (4 minutes), and thrombi grew very efficiently (bright thrombi). However, thrombi were not stable. They were often stripped off the vessel wall by blood flow (two sequential panels at 17 minutes) and ultimately led to a downstream occlusion (20 minutes with fluorescent platelets suspended in stagnant blood). The arrow in this panel (Fg–/–, 20 minutes) shows a thrombus formed in a neighboring venule. In the double-knockout mice (vWF/Fg–/–), very few fluorescently labeled platelets were seen on the vessel wall at an early time point (4 minutes), but delayed thrombus formation occurred with frequent embolization (two sequential panels at 27 minutes). The majority of the double-deficient arterioles eventually occluded.

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

Sign up for email alerts

Referenced in 4 patents
147 readers on Mendeley
See more details