Removing plasmin from the equation: something to chew on…

Morrow, Gael B.; Mutch, Nicola J.

Abstract

Thrombolytics or fibrinolytics are a group of pharmacological agents used to target and dissolve occlusive intravascular thrombi. Thrombi form a haemostatic plug at the site of injury to arrest bleeding and are essential for wound healing. However, intravascular thrombi that aberrantly form in pathophysiological settings block blood vessels lead to disturbed blood flow, thereby promoting thromboembolic events. Degradation of a thrombus occurs when the circulating zymogen, plasminogen, is cleaved to an active serine protease, plasmin. This process, termed fibrinolysis, is dependent on the presence of plasminogen activators; namely tissue plasminogen activator or urokinase (tPA or uPA, respectively). The differences in the mechanism of action of tPA and uPA are also important, tPA requires fibrin as a co‐factor to form a tertiary complex with plasmin, however, uPA does not and can promote plasmin generation in solution or on the cell surface. tPA is also more susceptible to plasminogen activator inhibitor 1 (PAI‐1) inhibition, as demonstrated by their second order rate constants, which differ by an order of magnitude; 12.6 × 107 vs. 4.8 × 106 M−1s−1 for tPA and uPA, respectively.

Citation

MORROW, G.B. and MUTCH, N.J. 2022. Removing plasmin from the equation: something to chew on… Journal of thrombosis and haemostasis [online], 20(2), pages 280-284. Available from: https://doi.org/10.1111/jth.15590

• Journal Article Type: Commentary
• Acceptance Date: Nov 10, 2021
• Online Publication Date: Jan 21, 2022
• Publication Date: Feb 28, 2022
• Deposit Date: Jul 25, 2023
• Publicly Available Date: Jul 25, 2023
• Journal: Journal of thrombosis and haemostasis
• Print ISSN: 1538-7933
• Electronic ISSN: 1538-7836
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 20
• Issue: 2
• Pages: 280-284
• DOI: https://doi.org/10.1111/jth.15590
• Keywords: Fibrin; HtrA1; Plasminogen; Tissue plasminogen activator; Thrombolytic therapy
• Public URL: https://rgu-repository.worktribe.com/output/2010422