Targeting platelet receptors in thrombotic and thrombo-inflammatory disorders

Summary

Platelet activation at sites of vascular injury is critical for the formation of a hemostatic plug which limits excessive blood loss, but also represents a major pathomechanism of ischemic cardio- and cerebrovascular diseases. Although currently available antiplatelet therapies have proved beneficial in preventing the recurrence of vascular events, their adverse effects on primary hemostasis emphasize the necessity to identify and characterize novel pharmacological targets for platelet inhibition. Increasing experimental evidence has suggested that several major platelet surface receptors which regulate initial steps of platelet adhesion and activation may become promising new targets for anti-platelet drugs due to their involvement in thrombotic and thrombo-inflammatory signaling cascades.

This review summarizes recent developments in understanding the function of glycoprotein (GP)Ib, GPVI and the C-type lectin-like receptor 2 (CLEC-2) in hemostasis, arterial thrombosis and thrombo-inflammation and will discuss the suitability of the receptors as novel targets to treat these diseases in humans.

Zusammenfassung

Die Aktivierung von Thrombozyten nach einer Gefäßverletzung ist essentiell für den Wundverschluss, um einen starken Blutverlust zu vermeiden, sie stellt allerdings auch einen Hauptpathomechanismus zur Entstehung von ischämischen kardio- und zerebrovaskulären Erkrankungen dar. Obwohl derzeit existierende antithrombotische Arzneimittel dem Auftreten solcher vaskulären Ereignisse vorbeugen, erfordern ihre ungünstigen Effekte auf die primäre Hämostase die Identifizierung und Charakterisierung neuer pharmako-logischer Angriffspunkte zur Thrombozytenhemmung. Experimentelle Studien weisen zunehmend darauf hin, dass einige zentrale Oberflächenrezeptoren der Thrombozyten, welche die ersten Schritte der Thrombozytenadhäsion und -aktivierung regulieren, möglicherweise viel versprechende neue Angriffspunkte für eine antithrombotische Therapie darstellen, da sie an thrombotischen und thrombo-inflammatorischen Signalwegen beteiligt sind.

Dieser Übersichtsartikel fasst jüngste Erkenntnisse im Verständnis der Funktion von Glykoprotein (GP)Ib, GPVI und C-type lectin-like receptor 2 (CLEC-2) in Hämostase, arterieller Thrombose und Thrombo-Inflammation zusammen und diskutiert die Eignung dieser Rezeptoren als neue antithrombotische Angriffspunkte.

Keywords

Platelets - thrombus formation - platelet receptors - antithrombotic target

Schlüsselwörter

Thrombozyten - Thrombusbildung - Thrombo- zytenrezeptoren - antithrombotischer Angriffs -punkt

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