Factor VII Activating Protease (FSAP) and Its Importance in Hemostasis—Part I: FSAP Structure, Synthesis and Activity Regulation: A Narrative Review
Abstract
:1. Prima Facie of Factor VII Activating Protease (FSAP)
1.1. Sites of FSAP Synthesis
1.2. FSAP Forms and Structure
1.3. FSAP Levels in Human Biological Samples
2. (Auto)activation and Activity Profile of FSAP
2.1. Enhancers and Inhibitors of FSAP Activation
2.1.1. Enhancers of scFSAP Activation
2.1.2. Inhibitors of scFSAP and Its Activation
2.2. Enhancers and Inhibitors of FSAP Activity
2.2.1. Enhancers of tcFSAP Activity
2.2.2. Inhibitors of tcFSAP and Its Activity
3. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Measurement | In Women | In Men | p-Value (Women vs. Men) * | References |
---|---|---|---|---|
FSAP levels | 11.15 µg/mL (3.60–16.43 µg/mL) | 10.51 µg/mL (4.36–16.15 µg/mL) | 0.07 | [33] |
97.4% | 87.5% | <0.001 | [34] | |
FSAP activity | 955 mPEU/mL (50–1453 mPEU/mL) | 841 mPEU/mL (290–1326 mPEU/mL) | 0.0005 | [33] |
81.1% | 68.7% | <0.001 | [34] | |
The ratio of percentage FSAP activity to percentage FSAP levels | 0.79 | 0.84 | <0.001 | [34] |
Name | Studies In Vitro Describing the Influence |
---|---|
Single-chain urokinase plasminogen activator (scuPA) | [38] |
Two-chain urokinase plasminogen activator (tcuPA) | [38] |
High molecular mass urokinase plasminogen activator (HMMuPA) | [38] |
Histones | [10] 1, [59,63,66,69,70,71] |
Nucleosomes (predigested) | [63] |
Chromatin | [59] |
Polyamines (spermidine, spermine, putrescine) | [9] |
Neutrophil extracellular traps (NETs) (disintegrated) | [71] |
Apoptotic and necrotic cells | [40,43,67,68] |
Poly-L-lysine (PLL) | [11,50] |
Polyethylenimine (PEI) | [50] |
Name | Studies In Vitro Describing the Influence | Contradictory Data |
---|---|---|
RNA | [9,10,26,51] | RNA was excluded as the cell-derived structure promoting FSAP activation [40,43]. RNA failed to promote FSAP activation in human plasma [10]. |
DNA | Effect at high levels of DNA [51] | Neither DNA homologue [26] nor DNA [66,71] was able to affect FSAP activation in vitro. |
Heparin | [9,10,11,17,18,38,48,51,52,53,64] | Heparin failed to promote FSAP activation in human plasma [10,59,65]. |
Low molecular weight heparin (LMWH) | Weak effect [48]. | LMWH inhibited spermidine-induced FSAP autoactivation in vitro [9]. |
Name | Studies In Vitro Describing the Influence | Contradictory Data |
---|---|---|
α-2-antiplasmin (AP) | [11] | FSAP-AP complexes are considered as the marker of completed FSAP activation [10,43,50,59,61,62,63,67,68,69,70,71]. |
C1-esteraze inhibitor (C1-inh) | [11] | FSAP-C1-inh complexes are considered as the marker of completed FSAP activation [43,67,70]. |
Plasminogen activator inhibitor type 1 (PAI-1) | Limited scFSAP-PAI-1 binding [39]. | Another experiment of the same authors indicated that scFSAP did not bind with PAI-1. |
Low molecular weight heparin (LMWH) | LMWH inhibited spermidine-induced FSAP autoactivation [9]. | LMWH weakly promotes FSAP activation [48]. |
Name | Studies In Vitro Describing the Influence | Contradictory Data |
---|---|---|
RNA | [73] | RNA increased inhibitor-driven reduction of tcFSAP activity [39]. |
DNA | Weak effect [73]. | DNA did not alter FSAP activity effectively [73]. |
Polyamines | Minimal effect [9]. | nd 1 |
Heparin | [3,18,25,28,42,46,48,52,73,74,75] | Heparin did not alter significantly FSAP activity [9,28,72,75] or FSAP activity was reduced in heparin presence [54]. Heparin increased inhibitor-driven reduction of tcFSAP activity [11,46,48,52]. |
Low molecular weight heparin (LMWH) | [48] | LMWH did not alter significantly FSAP activity [28]. LMWH increased inhibitor-driven reduction of tcFSAP activity [48]. |
Name | Studies In Vitro Describing the Influence |
---|---|
α-2-antiplasmin (AP) | [2,10] 1, [11,39], [43] 1, [46,50], [59] 1, [61,62,63] 1, [67,68,69,70,71] |
Plasminogen activator inhibitor-1 (PAI-1) | [39] 1, [48,52,72] |
Protease nexin-1 (PN-1) | [72,73] |
Antithrombin (AT) + heparin | [11,46,48] |
Name | Studies In Vitro Describing the Influence | Contradictory Data |
---|---|---|
Heparin | [11,46,48,52] | Heparin promoted [3,18,25,28,42,46,48,52,73,74,75] or did not alter FSAP activity [9,28,72,75]. Heparin did not promote PAI-1-driven inhibition of FSAP [39]. |
Low molecular weight heparin (LMWH) | [48] | LMWH did not alter significantly [28] or increased tcFSAP activity [48]. |
C1-esterase inhibitor (C1-inh) | [2,6,39,43] 1, [46,67,70] | Murine plasma levels of tcFSAP-C1-inh complexes were insignificant after histone injection [10]. |
Tissue factor pathway inhibitor (TFPI) | [67] | TFPI failed to inhibit tcFSAP activity [46]. |
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Kwiatkowska, I.; Żekanowska, E.; Lattanzi, S.; Alexandre, A.M.; Kister-Kowalska, A.; Słomka, A. Factor VII Activating Protease (FSAP) and Its Importance in Hemostasis—Part I: FSAP Structure, Synthesis and Activity Regulation: A Narrative Review. Int. J. Mol. Sci. 2023, 24, 5473. https://doi.org/10.3390/ijms24065473
Kwiatkowska I, Żekanowska E, Lattanzi S, Alexandre AM, Kister-Kowalska A, Słomka A. Factor VII Activating Protease (FSAP) and Its Importance in Hemostasis—Part I: FSAP Structure, Synthesis and Activity Regulation: A Narrative Review. International Journal of Molecular Sciences. 2023; 24(6):5473. https://doi.org/10.3390/ijms24065473
Chicago/Turabian StyleKwiatkowska, Iga, Ewa Żekanowska, Simona Lattanzi, Andrea M. Alexandre, Agata Kister-Kowalska, and Artur Słomka. 2023. "Factor VII Activating Protease (FSAP) and Its Importance in Hemostasis—Part I: FSAP Structure, Synthesis and Activity Regulation: A Narrative Review" International Journal of Molecular Sciences 24, no. 6: 5473. https://doi.org/10.3390/ijms24065473