Abstract 3046: Platelet-derived Microparticles Are a Novel Surrogate Marker for Activation of Leukocyte Integrin Mac-1 in Stent-induced Inflammation
Background: Inflammation as well as platelet activation at the site of local vessel-wall injury plays an essential role in the process of atherogenesis, plaque vulnerability and restenosis. Platelet-derived microparticles (PDMPs) released from activated platelets are not only a marker for platelet activation but also have procoagulant activity, and thereby, contribute to thrombus formation. In addition, PDMPs participate in the inflammatory process as a mediator of platelet-leukocyte, leukocyte-endothelial cell or leukocyte-leukocyte interactions. PDMPs stimulate cytokine productions and enhance the expression of cell adhesion molecules including leukocyte integrin Mac-1 (CD11b/CD18) that has an essential role in the mechanism of restenosis. The purpose of this study was to establish the clinical significance of circulating PDMPs measured by ELISA in pathophysiology of the inflammatory process after PCI.
Methods: We serially measured circulating PDMPs by ELISA in 35 patients undergoing coronary stenting. Simultaneously, high-sensitive C-reactive protein (hs-CRP) was measured by ELISA and binding of 8B2 that recognizes activation-dependent neoepitope of Mac-1 on the surface of neutrophils was analyzed by flow cytometry.
Results: PDMPs, hs-CRP and 8B2 binding increased after coronary stenting in a time-dependent manner with the maximum response at 48 hr in coronary sinus blood (PDMPs: 10.2±5.7 to 30.4±14.6 U/ml; P<0.001, hs-CRP: 0.26±0.22 to 1.51±0.88 mg/dl; P<0.001, activated Mac-1, 138±17% relative increase, P<0.001). PDMPs were correlated with hs-CRP (R=0.58, P<0.001) and the relative increase in 8B2 binding (R=0.69, P<0.001) 48 hrs after coronary stenting. Multiple regression analysis showed that each of PDMPs (R=0.40, P<0.05), hs-CRP (R=0.33, P<0.05) and the relative increase in 8B2 binding (R=0.48, P<0.01) was an independent predictor of the late lumen loss.
Conclusions: Coronary stenting enhanced circulating PDMPs in association with an inflammatory response in the injured vessel wall. PDMPs may be a useful marker for evaluation of stent-induced inflammatory status and a sound surrogate marker for activated Mac-1 to predict restenosis.