Platelet factor XIII-A regulates platelet function and promotes clot retraction and stability.
Platelet factor XIII-A regulates platelet function and promotes clot retraction and stability.
复制标题
血小板因子ⅩⅢ - A调节血小板功能,促进血块回缩及稳定性。
DOI:
10.1016/j.rpth.2023.100200
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发表时间:
2023-07
影响因子:
4.6
通讯作者:
Jones, Christopher I.
中科院分区:
文献类型:
--
作者:
Mitchell, Joanne L.;Little, Gemma;Bye, Alexander P.;Gaspar, Renato S.;Unsworth, Amanda J.;Kriek, Neline;Sage, Tanya;Stainer, Alexander;Sangowawa, Ibidayo;Morrow, Gael B.;Bastos, Ricardo N.;Shapiro, Susan;Desborough, Michael J. R.;Curry, Nicola;Gibbins, Jonathan M.;Whyte, Claire S.;Mutch, Nicola J.;Jones, Christopher I.
Factor XIII (FXIII) is an important proenzyme in the hemostatic system. The plasma-derived enzyme activated FXIII cross-links fibrin fibers within thrombi to increase their mechanical strength and cross-links fibrin to fibrinolytic inhibitors, specifically α2-antiplasmin, to increase resistance to fibrinolysis. We have previously shown that cellular FXIII (factor XIII-A [FXIII-A]), which is abundant in the platelet cytoplasm, is externalized onto the activated membrane and cross-links extracellular substrates. The contribution of cellular FXIII-A to platelet activation and platelet function has not been extensively studied. This study aims to identify the role of platelet FXIII-A in platelet function. We used normal healthy platelets with a cell permeable FXIII inhibitor and platelets from FXIII-deficient patients as a FXIII-free platelet model in a range of platelet function and clotting tests. Our data demonstrate that platelet FXIII-A enhances fibrinogen binding to the platelet surface upon agonist stimulation and improves the binding of platelets to fibrinogen and aggregation under flow in a whole-blood thrombus formation assay. In the absence of FXIII-A, platelets show reduced sensitivity to agonist stimulation, including decreased P-selectin exposure and fibrinogen binding. We show that FXIII-A is involved in platelet spreading where a lack of FXIII-A reduces the ability of platelets to fully spread on fibrinogen and collagen. Our data demonstrate that platelet FXIII-A is important for clot retraction where clots formed in its absence retracted to a lesser extent. Overall, this study shows that platelet FXIII-A functions during thrombus formation by aiding platelet activation and thrombus retraction in addition to its antifibrinolytic roles. Platelet factor XIII-A (FXIII-A) is present in abundance inside platelets. This study examines and characterises the roles of FXIII-A in platelet activation. Platelet FXIII-A regulates platelet activation and platelet sensitivity to stimulation. Platelet FXIII-A is involved in regulating blood clot compaction and clot stability.
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影响因子:
10.1
作者:
Mattheij, Nadine J. A.;Swieringa, Frauke;Cosemans, Judith M. E. M.
通讯作者:
Cosemans, Judith M. E. M.
DOI:
10.1083/jcb.118.6.1421
发表时间:
1992-09
期刊:
The Journal of cell biology
影响因子:
--
作者:
Hartwig JH
通讯作者:
Hartwig JH
DOI:
10.1016/0304-4165(80)90386-4
发表时间:
1980-01-01
期刊:
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子:
--
作者:
COHEN, I;BLANKENBERG, TA;VEIS, A
通讯作者:
VEIS, A
影响因子:
10.4
作者:
Calaminus, S. D. J.;Thomas, S.;Watson, S. P.
通讯作者:
Watson, S. P.
DOI:
10.1083/jcb.200703185
发表时间:
2007-11-05
期刊:
The Journal of cell biology
影响因子:
--
作者:
Flevaris P;Stojanovic A;Gong H;Chishti A;Welch E;Du X
通讯作者:
Du X