The Marburg I (MRI) single nucleotide polymorphism (SNP) of the factor VII-activating protease (FSAP) gene has been associated with thrombophilia, thromboembolism, atherosclerosis, and the incidence and progression of carotid stenosis. At present, MRI SNP testing is mainly performed using costly nucleic acid analysis. to assess the FSAP genotype.
The authors have developed an ELISA using antibodies [...]
Hyaluronic Acid Binding Protein 2 (synonym for factor VII-activating protease, FSAP) expression and activity are upregulated in the lungs of patients with acute respiratory distress syndrome, a disease with prominent vascular leakiness. The authors examined the role of HABP2 in vascular integrity using in vitro models of pulmonary EC barrier function and in vivo models of [...]
Daniel and colleagues asked whether FSAP may influence factors involved in pericellular proteolysis. They studied the influence of FSAP on the expression of uPA, tPA, MMP-2 and -9 (gelatinases) in cultured endothelial cells (EC) and vascular smooth muscle cells (VSMC). Studies were also performed in the mouse vascular injury model.
FSAP was found to activate pro-uPA [...]
Stavenuiter and colleagues produced recombinant FSAP (recFSAP) and analysed its suitability for functional studies.
In the recFSAP, the natural activation site (R313-I314) was replaced by a cleavage site for the bacterial protease thermolysin, which prevented the problem of autoactivation and autodegradation observed in natural FSAP. This allowed to otain purified intact FSAP.
Thermolysin activated recFSAP displayed the [...]
Factor VII-activating protease (FSAP) removes nucleosomes from apoptotic cells and is inhibited by C1-inhibitor (C1Inh) and 2-antiplasmin (AP).
The authors compared FSAP activation in the presence of apoptotic vs. non-apoptotic cells. FSAP in plasma was found to be activated upon incubation with apoptotic cells as evidenced by appearance of two-chain FSAP on western blots. No FSAP [...]
Etscheid and colleagues have further addressed the dual role of FSAP in hemostasis and fibrinolysis. With refined methods they compared the activities of FSAP wild-type (FSAP-wt) vs. FSAP variant Marburg I (FSAP-MI).
pro-uPA was found to be cleaved much more efficiently and at lower concentrations than FVII, indicating a preference of FSAP for the fibrinolytic system. [...]
The etiology of venous thromboembolic disease (VTE) has been the subject of several recent discoveries, particularly on genetic predisposing factors. Inherited deficiencies of coagulation proteins, such as Factor V Leiden and prothrombin G20210A, explain a small fraction of VTE. Other coagulation abnormalities are likely to contribute to the development of VTE.
The authors analysed the association [...]
Factor VII Activating Protease (FSAP) has been implied in the progression of atherosclerosis, and particularly in coronary artery disease, and the development of associated clinical events.
Along these lines Parahuleva and colleagues examined the relation between plasma concentration of FSAP and pro-inflammatory activation of macrophages and the signalling pathways induced by FSAP.
FSAP treatment induced IkappaB-dependent NF-kappaB [...]
Muhl et al have -for the first time- produced recombinant FSAP and its variants, and studied the regulation of the proteolytic activity of FSAP.
Over-expression of enzymatically active FSAP in HEK-293 cells decreased the cell viability; FSAP seems to have an intracellular function in regulating cell death, possibly via its ability to bind nucleic acids. Expression [...]
In the following four publications, the pro-uPA activating activity and Factor VII activating activity of FSAP, as well as its auto-activation and activation by uPA was described.
Based on these activities a role of FSAP in the hemostatic system has been suggested.
Authors and Source:
Römisch et al., Blood Coagul Fibrinolysis. 1999 Dec;10(8):471-479
Title:
A protease isolated from human plasma [...]
Wednesday, February 2, 2011
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