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P-selectin in arterial thrombosis

P-Selektin bei arterieller Thrombose

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Zusammenfassung

P-Selektin ist ein transmembranöses Protein, das in den α-Granula der Thrombozyten und den Weibel-Palade-Körperchen der Endothelzellen gespeichert ist. Nach Aktivierung dieser Zellen wird es rasch zur Zelloberfläche transportiert. Eine erhöhte Expression von P-Selektin auf Thrombozyten findet sich bei Erkrankungen, die mit arterieller Thrombose einhergehen, wie der koronaren Herzerkrankung, dem akuten Myokardinfarkt, dem Schlaganfall und der peripheren arteriellen Verschlusskrankheit. P-Selektin vermittelt einerseits das Rollen von Thrombozyten und Leukozyten auf aktivierten Endothelzellen, andererseits Interaktionen von Thrombozyten mit Leukozyten. Durch eine Interaktion mit P-Selektin-Glykoprotein-Ligand-1 (PSGL-1) bewirkt thrombozytäres P-Selektin die Bildung von Thrombozyten-Leukozyten-Aggregaten. Diese Interaktion von P-Selektin mit PSGL-1 induziert weiterhin eine vermehrte Produktion von ‘tissue factor’, verschiedenen Zytokinen und prokoagulativen Mikropartikeln in Leukozyten und unterstützt somit einen prothrombotischen Zustand. P-Selektin kommt auch eine Rolle in Thrombozyten-Thrombozyten-Interaktionen zu. Die resultierende Thrombozytenaggregation stellt einen wichtigen Faktor in der arteriellen Thrombose dar. P-Selektin interagiert mit thrombozytären Sulfatiden und stabilisiert so initiale Thrombozytenaggregate, die durch GPIIb/IIIa-Fibrinogen- Brücken vernetzt wurden. Eine Inhibition dieser P-Selektin-Sulfatid-Interaktionen führt zu einer Auflösung von Thrombozytenaggregaten. Somit spielt P-Selektin auch eine wichtige Rolle in der Thrombozyten- und Thrombozyten-Leukozyten-Aggregation—beides wichtige Mechanismen in der Entstehung einer arteriellen Thrombose.

Summary

P-selectin is a transmembrane protein present in the α granules of platelets and the Weibel-Palade bodies of endothelial cells. Following activation, it is rapidly translocated to the cell surface. P-selectin expression in platelets has been shown to be elevated in disorders associated with arterial thrombosis such as coronary artery disease, acute myocardial infarction, stroke, and peripheral artery disease. P-selectin mediates rolling of platelets and leukocytes on activated endothelial cells as well as interactions of platelets with leukocytes. Platelet P-selectin interacts with P-selectin glycoprotein ligand-1 (PSGL-1) on leukocytes to form platelet-leukocyte aggregates. Furthermore, this interaction of P-selectin with PSGL-1 induces the upregulation of tissue factor, several cytokines in leukocytes and the production of procoagulant microparticles, thereby contributing to a prothrombotic state. P-selectin is also involved in platelet-platelet interactions, i. e. platelet aggregation which is a major factor in arterial thrombosis. P-selectin interacts with platelet sulfatides, thereby stabilizing initial platelet aggregates formed by GPIIb/IIIa-fibrinogen bridges. Inhibtion of the P-selectin-sulfatide interaction leads to a reversal of platelet aggregation. Thus, P-selectin plays a significant role in platelet aggregation and platelet- leukocyte interactions, both important mechanisms in the development of arterial thrombosis.

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  1. Herzzentrum, Medizinische Klinik III, Kardiologie und Angiologie, Universitätsklinik Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany

    M. Merten

  2. Department of Pathology and Medicine, Baylor College of Medicine, VAMC #113, 2002 Holcombe Blvd, Houston TX77030, USA

    P. Thiagarajan

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Merten, M., Thiagarajan, P. P-selectin in arterial thrombosis. Z Kardiol 93, 855–863 (2004). https://doi.org/10.1007/s00392-004-0146-5

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