Die Rolle von Thrombin in der Blutgefäßentwicklung

Zusammenfassung

Die Bildung des Blutgefäßsytems ist ein entscheidender Schritt in der Embryonalentwicklung. Blutgefäßsystem und Blut entwickeln sich in enger räumlicher Nachbarschaft. In dieser Übersichtsarbeit wird die Rolle des Blutgerinnungssystems, inbesondere von Thrombin, als Koordinator der Blutgefäßbildung diskutiert.

In Mausmodellen zeigt sich, dass der Verlust von Gerinnungsfaktoren zu verminderter Thrombinbildung führt und von einer gestörten kardiovaskulären Entwicklung begleitet ist. Ähnliche Phänotypen lassen sich in Tiermodellen beobachten, in denen die Bindung von Thrombin und seinen Zelloberflächenrezeptor PAR-1 oder die anschließende G-Protein-Signalkaskade gestört sind. Darüber hinaus wird deutlich, dass die Thrombinsignalübertragung in der Blutgefäßentwicklung nicht durch das klassische Modell der extrinsischen und intrinsischen Blutgerinnungskaskade erklärbar sind, sondern zahlreiche Quervernetzungen bestehen. Da embryonale und adulte Blutgefäßbildung ähnlichen Mechanismen folgen, ist es entscheidend diese zu verstehen, um neuartige vaskuläre Therapiestrategien entwickeln zu können.

Summary

The formation of vasculature is a key step during embryogenesis. The vasculature and the intravascular blood compartment, which uses the former as a means of transportation, develop in a close spatial and temporal relationship. This review discusses the role of the blood coagulation system, particularly thrombin, as a tool to coordinate blood vessel formation. Mouse models indicate that a lack of coagulation factors results in impaired thrombin generation and consequently display a phenotype of disturbed cardiovascular development. Similar phenotypes are present in mouse models of impaired thrombin binding to its cellular receptor PAR1 or of disrupted signaling via G-proteins. Moreover, there is compelling evidence that thrombin signaling in vascular development cannot be explained by a model based only on the classical extrinsic and intrinsic coagulation pathways. As angiogenesis in adults follows the same signaling patterns as in embryos, it is of importance to learn about these pathways, hoping that they may serve as therapeutic targets in cardiovascular disease.

Schlüsselwörter

Thrombin - Blutgefäßbildung - PAR

Keywords

Thrombin - blood vessel formation - PAR

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