PPACK attenuates plasmin-induced changes in endothelial integrity

Thromb Res. 1993 Jun 15;70(6):425-36. doi: 10.1016/0049-3848(93)90085-3.


In order to determine whether plasmin affects endothelial cell integrity directly, confluent bovine aortic endothelial cells were treated with plasminogen and a plasminogen activator. The permeability of the monolayer to [125I]-albumin was shown to be increased significantly (P < 0.01) with a concomitant decrease in viability. Plasmin activity correlated significantly with endothelial cell permeability (p < 0.004; r = 0.82). Coincubation with D-phenylalanyl-L-prolyl-L-arginyl chloromethylketone, a tripeptide inhibitor of plasmin, reduced the increase in endothelial permeability induced by plasmin by 59% (p = 0.033). Monolayers studied in parallel were stained with rhodamine-phalloidin to visualize F-actin. There were significant morphologic changes in the endothelial monolayers exposed to plasmin compared to control monolayers, and these changes could be attenuated by coincubation with D-phenylalanyl-L-prolyl-L-arginyl chloromethylketone. These studies show that: 1) plasmin induces significant increases in endothelial cell permeability with accompanying morphologic changes; and 2) these deleterious functional and morphologic effects can be attenuated by coincubation with the plasmin inhibitor, D-phenylalanyl-L-prolyl-L-arginyl chloromethylketone.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / analysis
  • Amino Acid Chloromethyl Ketones / pharmacology*
  • Amino Acid Sequence
  • Animals
  • Antifibrinolytic Agents / pharmacology*
  • Cattle
  • Cell Membrane Permeability / drug effects
  • Cells, Cultured
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Fibrinolysin / antagonists & inhibitors*
  • Fibrinolysin / biosynthesis
  • Fibrinolytic Agents / pharmacology*
  • Molecular Sequence Data


  • Actins
  • Amino Acid Chloromethyl Ketones
  • Antifibrinolytic Agents
  • Fibrinolytic Agents
  • Fibrinolysin
  • phenylalanyl-prolyl-arginine-chloromethyl ketone