Preview

PDF 343Kb

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 Type:	Refereed Article
Keywords:	enzyme kinetics
Research Division:	Information and Computing Sciences
Research Group:	Artificial intelligence
Research Field:	Modelling and simulation
Objective Division:	Expanding Knowledge
Objective Group:	Expanding knowledge
Objective Field:	Expanding knowledge in the information and computing sciences
UTAS Author:	Tenekedjiev, K (Professor Kiril Tenekedjiev)
ID Code:	127970
Year Published:	2004
Web of Science® Times Cited:	10
Deposited By:	Governance Office
Deposited On:	2018-08-26
Last Modified:	2018-09-10
Downloads:	117 View Download Statistics