P-Selectin- and CD63-Exposing Platelet Microparticles Reflect Platelet Activation in Peripheral Arterial Disease and Myocardial Infarction

Abstract

Background: Platelet-derived microparticles (PMPs) are generally considered a marker of platelet activation in cardiovascular disease. We studied the extent to which PMP subpopulations parallel platelet activation in vitro and in vivo. Methods: Using flow cytometry, we analyzed PMP subpopulations from resting and activated platelets in vitro (n ‫؍‬ 6) as well as from plasma samples of patients with stable angina, peripheral arterial disease, or myocardial infarction [non-ST-elevation (NSTEMI) and ST-elevation (STEMI)] and from older, age-and sexmatched and young healthy individuals [n ‫؍‬ 10 for all groups except NSTEMI (n ‫؍‬ 11)]. Coagulation markers prothrombin fragment F 1 ؉ 2 and thrombin-antithrombin complexes were determined by ELISA. The PMPassociated fraction of soluble (s)P-selectin was estimated by ELISA. Results: In vitro, stimulation of platelets with thrombin receptor-activating peptide (15 mol/L) or the calcium ionophore A23187 (2.5 mol/L) increased fractions of both platelets and PMPs exposing P-selectin or CD63 (P <0.001 for all). Whereas the number of PMPs released by A23187-stimulated platelets increased significantly (P <0.001), the number of PMPs released from thrombin receptor-activating peptide-stimulated platelets remained constant (P >0.05). Ex vivo, numbers of circu-

Platelet microparticles inhibit IL-17 production by regulatory T cells through P-selectin

“…Like their parental cells, PMPs are involved in hemostasis, maintenance of vascular health, and immunity. 3,6,21,23,29,30,42 Here, we report that PMPs have the capacity to prevent the differentiation of Tregs into IL-17-and IFN-g-producing cells, even in the presence of proinflammatory cytokines. The mechanism of action consists of rapid and selective P-selectin-dependent binding of PMPs to a specialized CCR6…”

“…Upon activation, platelets typically expose the adhesion molecule P-selectin, which they can pass onto the PMPs they generate. 29 Like their parental cells, PMPs are able to bind immune cells expressing the P-selectin ligand P-selectin glycoprotein ligand-1 (PSGL-1). 30 This led us to investigate whether P-selectin is involved in the observed PMP adhesion to Tregs and/or the inhibition of their differentiation.…”

Oxidative alterations during human platelet storage

“…PAC-1 has been used identifying fibrinogen receptor GpIIb/IIIa in activated platelets (22). Additionally, P-selectin is only expressed on the platelet surface after α-granule secretion thus after activation (23). Recent studies proved that the increased expression of the P-selectin correlates with the in vivo recovery of transfused platelets (24).…”

Cell-Derived Microparticles in the Pathogenesis of Cardiovascular Disease

“…[3][4][5] Accordingly, in patients with acute myocardial infarction, elevated numbers of microparticles are present compared with healthy controls. 3,6,7 Moreover, subtypes of microparticles differ between patients with stable angina and those with acute coronary syndromes or myocardial infarction. 7,8 Earlier, it was demonstrated that microparticles from patients with myocardial infarction cause endothelial dysfunction and might contribute to the general vasomotor dysfunction observed after myocardial infarction.…”