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Keywords = recombinant FXIII

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16 pages, 4455 KB  
Article
Effect of Alpha2-Plasmin Inhibitor C-Terminal Heterogeneity on Clot Lysis and Clot Structure
by Réka Bogáti, Barbara Baráth, Dóra Pituk, Rita Orbán-Kálmándi, Péter Szűcs, Zoltán Hegyi, Zsuzsanna Bereczky, Zsuzsa Bagoly and Éva Katona
Biomolecules 2025, 15(8), 1127; https://doi.org/10.3390/biom15081127 - 5 Aug 2025
Viewed by 913
Abstract
Alpha2-plasmin inhibitor (α2PI) has a heterogeneous structure due to proteolytic cleavages in the circulation. The C-terminally cleaved form loses the plasminogen binding site and is, therefore, a slow plasmin inhibitor (NPB-α2PI). As FXIII primarily crosslinks the plasminogen-binding intact form (PB-α2PI) to fibrin, the [...] Read more.
Alpha2-plasmin inhibitor (α2PI) has a heterogeneous structure due to proteolytic cleavages in the circulation. The C-terminally cleaved form loses the plasminogen binding site and is, therefore, a slow plasmin inhibitor (NPB-α2PI). As FXIII primarily crosslinks the plasminogen-binding intact form (PB-α2PI) to fibrin, the effect of NPB-α2PI on fibrinolysis has been less studied. Herein, we investigated the effect of C-terminal truncation. Total-, PB-, and NPB-α2PI antigen levels and α2PI incorporation were measured by ELISAs from samples of 80 healthy individuals. Clot lysis parameters of the same subjects were investigated using an in vitro clot lysis assay. α2PI incorporation into the clot was demonstrated by Western blotting. Clot lysis and clot structure were also analyzed using an α2PI-deficient plasma substituted with recombinant PB- and NPB-α2PI. Both plasma and clot-bound levels of total- and NPB-α2PI showed a significant positive correlation with clot lysis parameters. NPB-α2PI was detected in the clot due to non-covalent binding. Regardless of the type of binding, both forms affected the clot structure by increasing the thickness of the fibrin fibers and reducing the pore size. In conclusion, we found that NPB-α2PI can bind non-covalently to fibrin, and this binding contributes to changes in clot structure and inhibition of fibrinolysis. Full article
(This article belongs to the Section Biomacromolecules: Proteins, Nucleic Acids and Carbohydrates)
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15 pages, 2254 KB  
Article
The Effect of Activated FXIII, a Transglutaminase, on Vascular Smooth Muscle Cells
by Réka Bogáti, Éva Katona, Amir H. Shemirani, Enikő Balogh, Helga Bárdos, Viktória Jeney and László Muszbek
Int. J. Mol. Sci. 2022, 23(10), 5845; https://doi.org/10.3390/ijms23105845 - 23 May 2022
Cited by 3 | Viewed by 3205
Abstract
Plasma factor XIII (pFXIII) is a heterotetramer of FXIII-A and FXIII-B subunits. The cellular form (cFXIII), a dimer of FXIII-A, is present in a number of cell types. Activated FXIII (FXIIIa), a transglutaminase, plays an important role in clot stabilization, wound healing, angiogenesis [...] Read more.
Plasma factor XIII (pFXIII) is a heterotetramer of FXIII-A and FXIII-B subunits. The cellular form (cFXIII), a dimer of FXIII-A, is present in a number of cell types. Activated FXIII (FXIIIa), a transglutaminase, plays an important role in clot stabilization, wound healing, angiogenesis and maintenance of pregnancy. It has a direct effect on vascular endothelial cells and fibroblasts, which have been implicated in the development of atherosclerotic plaques. Our aim was to explore the effect of FXIIIa on human aortic smooth muscle cells (HAoSMCs), another major cell type in the atherosclerotic plaque. Osteoblastic transformation induced by Pi and Ca2+ failed to elicit the expression of cFXIII in HAoSMCs. EZ4U, CCK-8 and CytoSelect Wound Healing assays were used to investigate cell proliferation and migration. The Sircol Collagen Assay Kit was used to monitor collagen secretion. Thrombospondin-1 (TSP-1) levels were measured by ELISA. Cell-associated TSP-1 was detected by the immunofluorescence technique. The TSP-1 mRNA level was estimated by RT-qPCR. Activated recombinant cFXIII (rFXIIIa) increased cell proliferation and collagen secretion. In parallel, a 67% decrease in TSP-1 concentration in the medium and a 2.5-fold increase in cells were observed. TSP-1 mRNA did not change significantly. These effects of FXIIIa might contribute to the pathogenesis of atherosclerotic plaques. Full article
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2 pages, 284 KB  
Case Report
Use of Catridecacog in a Patient with Severe Factor XIII Deficiency Undergoing Surgery
by Gianluca Sottilotta, Francesca Luise, Vincenzo Oriana, Angela Piromalli, Rosa Santacroce and Alessandra Di Lelio
Hematol. Rep. 2019, 11(1), 7912; https://doi.org/10.4081/hr.2019.7912 - 19 Feb 2019
Cited by 2 | Viewed by 750
Abstract
Despite many articles regarding the antihemorrhagic treatment and prophylaxis, there is a lack of experience about how to best conduct major surgical procedures in patients with congenital factor XIII (FXIII) deficiency. Here we report a case of surgery (right inguinal hernia, complicated by [...] Read more.
Despite many articles regarding the antihemorrhagic treatment and prophylaxis, there is a lack of experience about how to best conduct major surgical procedures in patients with congenital factor XIII (FXIII) deficiency. Here we report a case of surgery (right inguinal hernia, complicated by heaviness and pain) performed in a patient with FXIII deficiency, receiving recombinant FXIII prophylaxis (Catridecacog 35 UI/kg every 28 ± 2 days). Our experience shows that Catridecacog can be used safely and effectively not only for continued prophylaxis but also in surgery and adds to the very limited body of evidence currently available on surgery in this bleeding disorder. Full article
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