The frequent Marburg I polymorphism impairs the pro-urokinase activating potency of the factor VII activating...

Area of Science:

• Biochemistry
• Hematology
• Molecular Biology

Background:

• Factor Seven Activating Protease (FSAP) is a serine protease with known roles in coagulation.
• FSAP is also identified as a potent activator of single-chain urokinase (scuPA), a key fibrinolytic enzyme.
• Previous studies indicated that a subset of healthy individuals exhibit reduced scuPA activation potential in their plasma.

Purpose of the Study:

• To investigate the impact of FSAP polymorphisms on scuPA activation and plasma fibrinolytic potential.
• To characterize the functional consequences of the FSAP Marburg I polymorphism (G511E) on coagulation and clot lysis.

Main Methods:

• Genomic DNA analysis to identify FSAP polymorphisms.
• Thrombelastography to assess coagulation and fibrinolysis in wild-type and mutant plasmas.
• Functional assays using purified FSAP pro-enzyme and scuPA.

Main Results:

• A specific FSAP single nucleotide polymorphism (G511E), designated FSAP Marburg I, was identified in 5-10% of healthy donors and correlated with reduced scuPA activation.
• Plasma from individuals with the FSAP Marburg I polymorphism exhibited significantly delayed clot lysis under specific activation conditions.
• FSAP-deficient plasma showed prolonged clot lysis times, which were reversed by the addition of purified FSAP pro-enzyme and scuPA.

Conclusions:

• FSAP plays a significant role in the scuPA-dependent fibrinolytic system.
• The FSAP Marburg I polymorphism can impair plasma fibrinolytic potential, potentially influencing hemostasis.
• These findings highlight the clinical relevance of FSAP genetic variations in regulating blood clot lysis.