(Circulation. 1997;96:2339-2347.)
© 1997 American Heart Association, Inc.
Articles |
Inhibition of Arterial Thrombosis by Recombinant Annexin V in a Rabbit Carotid Artery Injury Model
From the Divisions of Hematology and Cardiology, Department of Internal Medicine, University of Texas Health Science Center, Houston.
Correspondence to Claude R. Benedict, MD, DPhil, Department of Internal Medicine, Division of Cardiology, MSB 6.039, University of Texas Medical School, 6431 Fannin St, Houston, TX 77030.
Background The procoagulant effect of anionic phospholipid may play a major role in the development of arterial thrombosis.
Methods and Results Annexin V, a
calcium-dependent anionic-phospholipid–binding protein, was
expressed and isolated from Escherichia coli and its
antithrombotic effect examined in a rabbit carotid artery thrombosis
model. A partially occlusive thrombus was formed in the left carotid
artery by application of electric current to produce an 
50%
occlusion of the lumen. After the current was discontinued, flow ceased
completely within 42±12 minutes (n=6) because of continuing
platelet/fibrin thrombus formation. When annexin V was given
at doses of 2.8 to 16.6
µg · kg-1 · min-1
for a period of 180 minutes, starting at the time the current was
stopped, there was a dose-dependent inhibition of thrombus formation.
At a dose of 5.6
µg · kg-1 · min-1,
blood flow remained patent throughout the infusion and for an
additional 60 minutes after the infusion was stopped. In addition,
there was a decrease in thrombus weight (16±7.4 versus 2.0±1.0 g),
125I-fibrin deposition (45% reduction,
P<.001), and 111In-labeled platelet
accumulation (43% reduction, P<.001). Prior mixing of
annexin V with phosphatidylserine micelles
abolished the antithrombotic effect of annexin V, whereas mixing with
phosphatidylcholine micelles had no effect. The antithrombotic effect
of annexin V was not associated with bleeding tendency, as judged by
the amount of blood absorbed in a gauze pad placed in a surgical
incision extending to the muscle tissue and by the standard template
bleeding time.
Conclusions These observations support a potentially important role for anionic phospholipid exposure in platelets in arterial thrombosis, and inhibition of this activity could be a novel target for therapy in coronary thrombosis and stroke and after angioplasty.
Key Words: annexins • thrombosis • phospholipids • hemodynamics
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