Plasma fibronectin promotes thrombus growth and stability in injured arterioles

Heyu Ni, Peter S.T. Yuen, Jessie M. Papalia, Jane E. Trevithick, Takao Sakai, Reinhard Fässler, Richard O. Hynes, Denisa D. Wagner

Research output: Contribution to journalArticlepeer-review

182 Citations (Scopus)

Abstract

Mice lacking both of the best-known platelet ligands, von Willebrand factor and fibrinogen, can still form occlusive thrombi in injured arterioles. The platelets of these animals accumulate excessive amounts of fibronectin (FN). These observations led us to examine the contribution of plasma FN (pFN) to thrombus formation. Inactivation of the FN gene in FN conditional knockout mice reduced pFN levels to <2% and platelet FN to ≈20% of the levels in similarly treated control mice. The mice were then observed in a model of arterial injury to evaluate their capacity to form thrombi. The deficiency of pFN did not affect the initial platelet adhesion, but a delay of several minutes in thrombus formation was observed in the arterioles of pFN-deficient mice as compared with control mice. The thrombi that formed in the absence of pFN were stably anchored to the vessel wall but continuously shed platelets or small platelet clumps, thus slowing their growth significantly; the platelet/platelet cohesion was apparently diminished. Consequently the occlusion of pFN-deficient vessels was delayed, with the majority of vessels remaining patent at the end of the 40-min observation period. We conclude that, in addition to von Willebrand factor and fibrinogen, FN plays a significant role in thrombus initiation, growth, and stability at arterial shear rates and that deficiency in each of the three platelet ligands has its own specific impact on platelet plug formation.

Original languageEnglish
Pages (from-to)2415-2419
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number5
DOIs
Publication statusPublished - 04-03-2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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