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Free fatty acids modulate thrombin mediated fibrin generation resulting in less stable clots

Citation

Tanka-Salamon, A and Komorowicz, E and Szabo, L and Tenekedjiev, K and Kolev, K, Free fatty acids modulate thrombin mediated fibrin generation resulting in less stable clots, PLoS One, 11, (12) Article e0167806. ISSN 1932-6203 (2016) [Refereed Article]


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Copyright: 2016 Tanka-Salamon et al. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

DOI: doi:10.1371/journal.pone.0167806

Abstract

Upon platelet activation, free fatty acids are released at the stage of thrombus formation, but their effects on fibrin formation are largely unexplored. Our objective was to characterize the kinetic effects of fatty acids on thrombin activity, as well as the structural and mechanical properties of the resultant fibrin clots. Thrombin activity on fibrinogen was followed by turbidimetry and detailed kinetic characterization was performed using a fluorogenic short peptide substrate. The viscoelastic properties of fibrin were measured with rotatory oscillation rheometer, whereas its structure was analyzed with scanning electron microscopy (SEM). In turbidimetric assays of fibrin generation, oleate and stearate at physiologically relevant concentrations (60600 μM) produced a bell-shaped inhibitory dose response, increasing 10- to 30-fold the time to half-maximal clotting. Oleate inhibited thrombin activity on a short peptide substrate according to a mixed-type inhibitor pattern (a 9-fold increase of the Michaelis constant, Km and a 20% decrease of the catalytic constant), whereas stearate resulted in only a minor (15%) drop in the catalytic constant without any change in the Km. Morphometric analysis of SEM images showed a 73% increase in the median fiber diameter in the presence of stearate and a 20% decrease in the presence of oleate. Concerning the viscoelastic parameters of the clots, storage and loss moduli, maximal viscosity and critical shear stress decreased by 3265% in the presence of oleate or stearate, but loss tangent did not change indicating decreased rigidity, higher deformability and decreased internal resistance to shear stress. Our study provides evidence that free fatty acids (at concentrations comparable to those reported in thrombi) reduce the mechanical stability of fibrin through modulation of thrombin activity and the pattern of fibrin assembly.

Item Details

Item Type:Refereed Article
Keywords:data processing to characterize kinetic effects of fatty acids on thrombin activity
Research Division:Mathematical Sciences
Research Group:Statistics
Research Field:Applied Statistics
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:113108
Year Published:2016
Deposited By:NC Maritime Engineering and Hydrodynamics
Deposited On:2016-12-13
Last Modified:2017-03-31
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