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Phospholipid barrier to fibrinolysis. Role for the anionic polar head charge and the gel phase crystalline structure

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posted on 2023-05-19, 20:44 authored by Varadi, B, Kolev, K, Kiril TenekedjievKiril Tenekedjiev, Meszaros, G, Kovalsky, I, Longstaff, C, Machovich, R
The massive presence of phospholipids is demonstrated in frozen sections of human arterial thrombi. Purified platelet phospholipids and synthetic phospholipids retard in vitro tissue-type plasminogen activator (tPA)-induced fibrinolysis through effects on plasminogen activation and plasmin function. The inhibition of plasminogen activation on the surface of fibrin correlates with the fraction of anionic phospholipid. The phospholipids decrease the amount of tPA penetrating into the clot by 75% and the depth of the reactive surface layer occupied by the activator by up to 30%, whereas for plasmin both of these parameters decrease by ∼50%. The phospholipids are not only a diffusion barrier, they also bind the components of the fibrinolytic system. Isothermal titration calorimetry shows binding characterized with dissociation constants in the range 0.35-7.64 μM for plasmin and tPA (lower values with more negative phospholipids). The interactions are endothermic and thermodynamically driven by an increase in entropy, probably caused by the rearrangements in the ordered gel structure of the phospholipids (in line with the stronger inhibition at gel phase temperatures compared with liquid crystalline phase temperatures). These findings show a phospholipid barrier, which should be overcome during lysis of arterial thrombi.

History

Publication title

Journal of Biological Chemistry

Volume

279

Issue

38

Pagination

39863-39871

ISSN

0021-9258

Department/School

Australian Maritime College

Publisher

American Society for Biochemistry and Molecular Biology, Inc.

Place of publication

USA

Rights statement

©2004 the American Society for Biochemistry and Molecular Biology. This research was originally published in the Journal of Biological Chemistry. Balazs Varadi, Krasimir Kolev, Kiril Tenekedjiev, Gyongyi Meszaros, Ilona Kovalszky, Colin Longstaff?, and Raymund Machovich. J. Biol. Chem. 2004; Vol 279, pp.39863–39871.

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Expanding knowledge in the health sciences; Expanding knowledge in the information and computing sciences

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