Effect of remnant-like particle on shear-induced platelet activation and its inhibition by antiplatelet agents

Abstract

Remnant-like particles (RLPs) have been reported to promote atherosclerosis and to have effects on platelet function. We studied the effects of RLP on shear-induced platelet activation and their inhibition by antiplatelet agents in vitro. RLP were separated using two monoclonal antibodies, anti apo B-100 and anti apo A-I. These RLP fractions were added to whole blood (WB) or platelet-rich plasma (PRP) in serial dilution of 1, 10 or 100 μg RLP triglyceride (TG) per ml of total sample volume. These samples were incubated, and then stimulated with a high shear stress of 108 dyn/cm 2. Shear-induced platelet aggregation (SIPA) was calculated from the percentage of single platelet loss. P-selectin expression on platelet surface and platelet-derived microparticle (PMP) generation were measured before and after stimulation with shear stress using flow cytometer. SIPA was significantly enhanced by RLP in WB but not in PRP. This enhancing effect was not dose-dependent and was greatest at 10 μg TG/ml. P-selectin expression induced by shear stress was only enhanced by RLP at a concentration of 100 μg TG/ml in both WB and PRP, while generation of PMP induced by shear stress was only enhanced by RLP at a concentration of 100 μg TG/ml in WB. Aspirin inhibited only the enhancement of SIPA by RLPs, while cilostazol inhibited the enhancement of not only SIPA but also p-selectin expression and PMP generation by RLPs.