Regulation of plasminogen activation on cell surfaces and fibrin

Journal of Thrombosis and Haemostasis : JTH
T UranoY Suzuki

Abstract

The fibrinolytic system dissolves fibrin and maintains vascular patency. Recent advances in imaging analyses allowed visualization of the spatiotemporal regulatory mechanism of fibrinolysis, as well as its regulation by other plasma hemostasis cofactors. Vascular endothelial cells (VECs) retain tissue-type plasminogen activator (tPA) after secretion and maintain high plasminogen (plg) activation potential on their surfaces. As in plasma, the serpin, plasminogen activator inhibitor type 1 (PAI-1), regulates fibrinolytic potential via inhibition of the VEC surface-bound plg activator, tPA. Once fibrin is formed, plg activation by tPA is initiated and effectively amplified on the surface of fibrin, and fibrin is rapidly degraded. The specific binding of plg and tPA to lytic edges of partly degraded fibrin via newly generated C-terminal lysine residues, which amplifies fibrin digestion, is a central aspect of this pathophysiological mechanism. Thrombomodulin (TM) plays a role in the attenuation of plg binding on fibrin and the associated fibrinolysis, which is reversed by a carboxypeptidase B inhibitor. This suggests that the plasma procarboxypeptidase B, thrombin-activatable fibrinolysis inhibitor (TAFI), which is activated by thr...Continue Reading

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Citations

Oct 26, 2018·Arteriosclerosis, Thrombosis, and Vascular Biology·Stéphane LoyauMartine Jandrot-Perrus
Dec 26, 2018·Journal of Thrombosis and Haemostasis : JTH·Valerie TutwilerJohn W Weisel
Jun 5, 2019·Expert Review of Hematology·Anetta Undas, Joanna Natorska
Oct 2, 2019·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·Maurizio MargaglioneAngela Bruna Maffione
Jul 17, 2019·Current Drug Targets·Tetsumei UranoFrancis J Castellino
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Aug 25, 2020·Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis·Hideo WadaKohji Okamoto
Mar 11, 2020·Experimental & Molecular Medicine·Haili LinPeng Xu
Feb 23, 2020·Wiener klinische Wochenschrift·Barbara Thaler
Jan 29, 2020·Research and Practice in Thrombosis and Haemostasis·Tetsumei Urano, Yuko Suzuki
Sep 16, 2020·Scientific Reports·Tori C BootpetchRegie Lyn P Santos-Cortez
Jul 2, 2019·Frontiers in Immunology·Subhradip MukhopadhyayToni M Antalis
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Jun 23, 2021·MBio·Hyun Jung JiPaul M Sullam
Nov 5, 2021·Journal of Thrombosis and Haemostasis : JTH·Ophira Salomon, David Gailani
Dec 14, 2021·Journal of Thrombosis and Haemostasis : JTH·Fahumiya SamadLindsey A Miles

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Methods Mentioned

BETA
X‐ray
confocal microscopy
imaging techniques

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