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Blood, 15 July 2001, Vol. 98, No. 2, pp. 368-373
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Increased thrombogenesis and embolus formation in mice lacking
glycoprotein V
Heyu Ni,
Vanitha Ramakrishnan,
Zaverio M. Ruggeri,
Jessie M. Papalia,
David R. Phillips, and
Denisa D. Wagner
From the Center for Blood Research and Department of
Pathology, Harvard Medical School, Boston, MA; COR Therapeutics, South
San Francisco, CA; and the Scripps Research Institute, La Jolla, CA.
The glycoprotein (GP) Ib-V-IX complex plays a critical role in
initiating platelet adhesion to von Willebrand factor (vWF) at the site
of vascular injury. The complex also forms a high-affinity binding site
for thrombin. Using an intravital microscopy mouse model, it was
previously established that vWF plays a critical role in mediating
platelet adhesion and thrombus formation following mesenteric
arteriolar injury induced by ferric chloride. Further characterization
of this model showed that these thrombotic events were also thrombin
dependent. Using this vWF- and thrombin-dependent model, this study
shows that GP V gene deficiency significantly accelerates
both platelet adhesion and thrombus formation in mice following
arteriolar injury. The time required for vessel occlusion in GP
V-deficient (GP V /) mice was significantly shorter
than that in wild-type mice. Interestingly, large emboli were also
produced in GP V/ mice, but not in wild-type mice,
causing frequent downstream occlusion. However, when the 2 genotypes
were compared in the in vitro perfusion chamber where thrombin was
inhibited by heparin, no significant differences were found in either
initial single-platelet adhesion or thrombus volume. These results
demonstrate that GP V/ mice have accelerated thrombus
growth in response to vascular injury and suggest that this is caused
by enhanced thrombin-induced platelet activation rather than enhanced
binding of GPIb-V-IX to vWF. Absence of GP V also compromises thrombus stability.
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