A new role for P-selectin in shear-induced platelet aggregation

Background-P-selectin, expressed on platelets on activation, mediates rolli ng of platelets on endothelial cells, but its role in shear-induced platele t aggregation is not known. Methods and Results-Platelets were exposed to either a single pulse (30 sec onds) or 3 pulses (10 seconds) of high shear stress (150 to 200 dynes/cm(2) ) each followed by low shear stress (10 dynes/cm2) for 4.5 minutes or 90 se conds, respectively, at 37 degreesC to resemble more closely in vivo condit ions such as those in stenotic arteries. Under these conditions, platelet a ggregation was significantly increased compared with low or high shear stre ss alone. Monoclonal anti-P-selectin antibodies inhibited shear-induced pla telet aggregation, especially when induced by the combination of high and l ow shear stress, by approximate to 70% and had an additive effect on the in hibition by abciximab (anti-glycoprotein (GP) Ilb/IIIa antibody). However, anti-P-selectin antibody inhibited shear-induced platelet aggregation only at 37 degreesC, not at 22 degreesC, whereas abciximab inhibited shear-induc ed platelet aggregation at both 22 degreesC and 37 degreesC. This different ial effect of anti-P-selectin antibody is explained by the finding that she ar-induced P-selectin expression on platelets was observed mainly at 37 deg reesC. Conclusions-These results indicate that pulsatile shear stress, which resem bles flow conditions in stenotic arteries, induces significantly more plate let aggregation at 37 degreesC than monophasic shear stress. Under these co nditions, we show a novel role for P-selectin in platelet aggregation disti nct from that of GP IIb/IIIa, which may be of importance in the initiation of thrombosis associated with atherosclerotic lesions.