Enhanced platelet-derived microparticle formation is associated with carotid atherosclerosis in convalescent stroke patients

Abstract

Platelets participate in the development and progression of atherosclerosis. During this process they interact with endothelial cells and leukocytes. Therefore, we investigated the associations between carotid atherosclerosis and platelet reactivity markers. The platelet surface expression of P-selectin (CD62P) and the activated GPIIb/IIIa receptor (corresponding to increased binding of PAC-1), as well as the fraction of platelet-derived microparticles (PMPs) prior to and after platelet stimulation with TRAP or ADP, were determined using flow cytometry in 94 subjects in the convalescent phase of ischaemic stroke and in 76 disease controls. The mean common carotid intima-media thickness (CCAmean IMT), maximal common carotid IMT (CCAmax IMT) and maximal bifurcation IMT (BIFmax IMT) were measured bilaterally using B mode, colour Doppler ultrasonography. In stroke subjects IMT within CCA and BIF were greater than in disease controls and the percentage of PMPs prior to and after ex vivo stimulation with agonists was significantly higher than in controls. Multiple regression analysis revealed that PMPs were positively and independently correlated with both CCAmean IMT ( β = 0.23; p < 0.01) and stroke ( β = 0.21; p<0.01), while PAC-1 binding to platelets activated with ADP was negatively and independently associated with CCAmean IMT ( β = −0.29; p<0.001) and atherosclerotic carotid plaque presence ( β = −0.28, p = 0.003). We found a positive association between enhanced PMP formation and atherosclerotic thickening of carotid intima-media or carotid plaque in patients after ischaemic stroke. We demonstrated that diminished expression of active GPIIb/IIIa in the ADP-activated platelets is associated with increased carotid IMT, independently of stroke.