(Circulation. 2000;102:2045.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
A New Role for P-Selectin in Shear-Induced Platelet Aggregation
From the Divisions of Cardiology (M.M.) and Hematology (P.T.), Department of Internal Medicine, University of Texas Houston Medical School, Houston, and the Department of Bioengineering, Rice University (T.C., D.H.), Houston, Tex.
Background—P-selectin, expressed on platelets on activation, mediates rolling of platelets on endothelial cells, but its role in shear-induced platelet aggregation is not known.
Methods and Results—Platelets were exposed to either a single
pulse (30 seconds) or 3 pulses (10 seconds) of high shear stress (150
to 200 dynes/cm2) each followed by low shear stress (10
dynes/cm2) for 4.5 minutes or 90 seconds, respectively, at
37°C to resemble more closely in vivo conditions such as those in
stenotic arteries. Under these conditions, platelet
aggregation was significantly increased compared with low or high shear
stress alone. Monoclonal anti–P-selectin antibodies inhibited
shear-induced platelet aggregation, especially when induced by the
combination of high and low shear stress, by 
70% and had an
additive effect on the inhibition by abciximab
(anti–glycoprotein (GP) IIb/IIIa antibody). However,
anti–P-selectin antibody inhibited shear-induced platelet
aggregation only at 37°C, not at 22°C, whereas abciximab inhibited
shear-induced platelet aggregation at both 22°C and 37°C. This
differential effect of anti–P-selectin antibody is explained by the
finding that shear-induced P-selectin expression on platelets was
observed mainly at 37°C.
Conclusions—These results indicate that pulsatile shear stress, which resembles flow conditions in stenotic arteries, induces significantly more platelet aggregation at 37°C than monophasic shear stress. Under these conditions, we show a novel role for P-selectin in platelet aggregation distinct from that of GP IIb/IIIa, which may be of importance in the initiation of thrombosis associated with atherosclerotic lesions.
Key Words: platelets • platelet-derived factors • glycoproteins • circulation • blood flow
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