Flow rate-modulated dissolution of fibrin with clot-embedded and circulating proteases

Erzsébet Komorowicz, K. Kolev, István Léránt, R. Machovich

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The efficiency of plasmin, miniplasmin, and neutrophil leukocyte elastase in fibrin digestion is well characterized in static systems. Since in vivo the components of the fibrinolytic system are permanently exposed to flow, we have developed two in vitro models and studied the effect of shear forces on fibrin dissolution with those proteases. Cylindrical nonocclusive fibrin clots are perfused at various flow rates through their preformed axial channel and dissolution of fibrin is followed by measuring the absorbance of degradation products released into the circulating fluid phase. In one experimental setting, fibrin surface is degraded with enzymes applied in the recirculating fluid phase; in another setting, clots containing gel-embedded proteases are perfused with enzyme-free buffer. As shear rate at fibrin surface is changed from 25 to 500 s-1, the rate of product release by recirculated enzymes increases 2.8-, 2.9-, and 4-fold for plasmin, miniplasmin, and porcine pancreatic elastase, respectively. Buffer-perfused fibrin containing gel-embedded plasmin or miniplasmin is disintegrated by shear forces at a relatively early stage of dissolution, and this disassembly is related to the formation of fragment Y (150 kDa) and fragment D (100 kDa) fibrin degradation products. Fibrin clots degraded by incorporated polymorphonuclear leukocyte elastase, which yields different degradation products, do not disassemble abruptly, even at the highest shear rate (500 s-1). Our results suggest that fibrin surface degradation is accelerated with increasing shear rate and that plasmin or miniplasmin embedded in the clot promotes the release of particular clot remnants into the circulating phase, whereas polymorphonuclear leukocyte elastase does not.

Original languageEnglish
Pages (from-to)1102-1108
Number of pages7
JournalCirculation Research
Volume82
Issue number10
Publication statusPublished - Jun 1 1998

Fingerprint

Fibrin
Peptide Hydrolases
Leukocyte Elastase
Fibrinolysin
Buffers
Enzymes
Gels
Fibrin Fibrinogen Degradation Products
Pancreatic Elastase
Digestion
Swine
miniplasmin

Keywords

  • Fibrinolysis
  • Polymorphonuclear leukocyte elastase
  • Protease
  • Shear rate
  • Thrombus

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Flow rate-modulated dissolution of fibrin with clot-embedded and circulating proteases. / Komorowicz, Erzsébet; Kolev, K.; Léránt, István; Machovich, R.

In: Circulation Research, Vol. 82, No. 10, 01.06.1998, p. 1102-1108.

Research output: Contribution to journalArticle

Komorowicz, Erzsébet ; Kolev, K. ; Léránt, István ; Machovich, R. / Flow rate-modulated dissolution of fibrin with clot-embedded and circulating proteases. In: Circulation Research. 1998 ; Vol. 82, No. 10. pp. 1102-1108.
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