Factor VII activating protease

Summary

Factor VII activating protease (FSAP) is a circulating serine protease with high homology to fibrinolytic enzymes. A role in the regulation of coagulation and fibrinolysis is suspected based on in vitro studies demonstrating activation of FVII or pro-urokinase plasminogen activator (uPA). However, considering the paucity of any studies in animal models or any correlative studies in humans the role of FSAP in haemostasis remains unclear. In relation to vascular remodeling processes or inflammation it has been convincingly shown that FSAP interacts with growth factors as well as protease activated receptors (PAR). Against this sparse background there are a plethora of studies which have investigated the linkage of single nucleotide polymorphisms (SNP) in the FSAP gene (HABP2) to various diseases. The G534E SNP of FSAP is associated with a low proteolytic activity due to an amino acid exchange in the protease domain. This and other SNPs have been linked to carotid stenosis, stroke as well as thrombosis in the elderly and plaque calcification. These SNP analyses indicate an important role for FSAP in the regulation of the haemostasis system as well as fibroproliferative inflammatory processes.

Zusammenfassung

Die Faktor-VII-aktivierende Protease (FSAP) ist eine plasmatische Protease mit struktureller Ähnlichkeit zu Enzymen des fibrinolytischen Systems. In-vitro-Untersuchungen zeigten, dass Faktor VII und Prourokinase (sc-uPA) aktiviert werden und weisen auf eine regulierende Funktion von FSAP in Blutgerinnung und Fibrinolyse hin. Aus Mangel an Studien im Tiermodell und im Menschen bleibt die Rolle der FSAP in der Hämostase ungeklärt. Bei Vorgängen der Gefäßumbildung und bei Entzündungsprozessen konnte gezeigt werden, dass FSAP mit Wachstumsfaktoren und Proteaseaktivierten Rezeptoren (PAR) wechselwirkt. Der Zusammenhang zwischen Einzelnukleotid-Polymorphismen (SNP) im FSAP-Gen (HABP-2) und verschiedenen kardiovaskulären Erkrankungen wurde durch zahlreiche Studien belegt. Der G534E-Polymorphismus in der Proteasedomäne ist verbunden mit der Abschwächung oder dem Verlust proteolytischer Aktivität der FSAP. Dieser und andere SNPs wurden mit Schlaganfall und Karotisstenose in Verbindung gebracht sowie mit der Thromboseneigung bei älteren Patienten und der Kalzifizierung atherosklerotischer Plaques. Diese SNP-Analysen weisen auf eine wichtige Rolle der FSAP in der Regulierung des Hämostasesystems und bei fibroproliferativen Entzündungsvorgängen hin.

Keywords

FSAP - growth factor - HABP2 - inflammation - remodelling - SNP - thrombosis

Schlüsselwörter

Entzündung - FSAP - Gefäßumbildung - HABP2 - SNP - Thrombose - Wachstumsfaktor

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