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

Citation

Varadi, B and Kolev, K and Tenekedjiev, K and Meszaros, G and Kovalsky, I and Longstaff, C and Machovich, R, Phospholipid barrier to fibrinolysis. Role for the anionic polar head charge and the gel phase crystalline structure, Journal of Biological Chemistry, 279, (38) pp. 39863-39871. ISSN 0021-9258 (2004) [Refereed Article]


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Copyright 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.3986339871.

DOI: doi:10.1074/jbc.M405172200

Abstract

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.

Item Details

Item Type:Refereed Article
Keywords:enzyme kinetics
Research Division:Information and Computing Sciences
Research Group:Artificial Intelligence and Image Processing
Research Field:Simulation and Modelling
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in the Information and Computing Sciences
Author:Tenekedjiev, K (Professor Kiril Tenekedjiev)
ID Code:127970
Year Published:2004
Web of Science® Times Cited:7
Deposited By:AMC Governance Office
Deposited On:2018-08-26
Last Modified:2018-09-10
Downloads:1 View Download Statistics

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